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Erschienen in: CardioVasc 6/2014

23.12.2014 | Schwerpunkt_Lipidologie

Neues von ESC und AHA

Perspektiven zu cholesterinwirksamer Behandlung 2014

verfasst von: Prof. Dr. med. Gerald Klose, Rainer Schulz, Wolfgang Koenig

Erschienen in: CardioVasc | Ausgabe 6/2014

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Zusammenfassung

Cholesterinwirksame Therapie ist eine Schlüsselmaßnahme in der Prävention kardiovaskulärer Erkrankungen. Dass dieses Kapitel der Gesundheitsversorgung mit der Statintherapie nicht abgeschlossen ist, wurde bei den diesjährigen großen internationalen Kardiologiekongressen sichtbar. Große Erwartungen an weitere Entwicklungen zur Erhöhung der Wirksamkeit cholesterinsenkender Behandlung lassen eine Vielzahl von Ergebnissen klinischer Programme mit den PCSK9-Inhibitoren erkennen. Schon kurze Zeit nach der Entdeckung klinischer Implikationen von PCSK9-Mutationen liegen größere Studien zu Wirkungen und Verträglichkeit monoklonaler Antikörper gegen PCSK9 vor. Der Beitrag führt in Erkenntnisse zur Funktion von PCSK9 ein und erlaubt eine Bewertung therapeutischer Wirkungen auf dem Boden einer systematischen Analyse bisher vorgestellter Studien. Die beträchtliche LDL-Cholesterin-senkende Potenz bei einem verblüffend guten Sicherheitsprofil weisen auf Behandlungsoptionen in klinischen Konstellationen, für die bislang „unmet needs“ bestehen.
Literatur
1.
Zurück zum Zitat Marchand F. Über Arteriosklerose (Atherosklerose), Verh Deutscher Kongress Inn Med. 1904;21:29–53. Marchand F. Über Arteriosklerose (Atherosklerose), Verh Deutscher Kongress Inn Med. 1904;21:29–53.
2.
Zurück zum Zitat Windaus A. Über den Gehalt normaler und atheromatöser Aorten an Cholesterin und Cholesterinestern. Hoppe Seylers Z Physiol Chem. 1910;67:174–6. Windaus A. Über den Gehalt normaler und atheromatöser Aorten an Cholesterin und Cholesterinestern. Hoppe Seylers Z Physiol Chem. 1910;67:174–6.
3.
Zurück zum Zitat Anitschkow N. Über die Veränderungen der Kaninchenaorta bei experimenteller Cholesterinsteatose. Beitr Pathol Anat. 1913;56:379–404. Anitschkow N. Über die Veränderungen der Kaninchenaorta bei experimenteller Cholesterinsteatose. Beitr Pathol Anat. 1913;56:379–404.
4.
Zurück zum Zitat Keys A, Menotti A, Karvonen MJ et al. The diet and 15-year death rate in the Seven Countries Study. Am J Epidemiol. 1986;124:903–15.PubMed Keys A, Menotti A, Karvonen MJ et al. The diet and 15-year death rate in the Seven Countries Study. Am J Epidemiol. 1986;124:903–15.PubMed
5.
Zurück zum Zitat Kannel WB, Bishop Lecture. Contribution of the Framingham Study to preventive cardiology, J Am Coll Cardiol. 1990;15:206–11.PubMed Kannel WB, Bishop Lecture. Contribution of the Framingham Study to preventive cardiology, J Am Coll Cardiol. 1990;15:206–11.PubMed
6.
Zurück zum Zitat Assmann G, Cullen P, Schulte H et al. The Münster Heart Study (PROCAM). Results of follow-up at 8 years. Eur Heart J. 1998;19 Suppl A:A2–11.PubMed Assmann G, Cullen P, Schulte H et al. The Münster Heart Study (PROCAM). Results of follow-up at 8 years. Eur Heart J. 1998;19 Suppl A:A2–11.PubMed
7.
Zurück zum Zitat Erdmann J, Linsel-Nitschke P, Schunkert H et al. Genetische Ursachen des Herzinfarktes: Neue Aspekte durch genomweite Assoziationsstudien Dtsch Arztebl Int. 2010;107:694–9. Erdmann J, Linsel-Nitschke P, Schunkert H et al. Genetische Ursachen des Herzinfarktes: Neue Aspekte durch genomweite Assoziationsstudien Dtsch Arztebl Int. 2010;107:694–9.
8.
Zurück zum Zitat Jørgensen AB, Frikke-Schmidt R, Nordestgaard BG et al. Loss-of-function mutations in APOC3 and risk of ischemic vascular disease. N Engl J Med. 2014;371:32–41.PubMed Jørgensen AB, Frikke-Schmidt R, Nordestgaard BG et al. Loss-of-function mutations in APOC3 and risk of ischemic vascular disease. N Engl J Med. 2014;371:32–41.PubMed
9.
Zurück zum Zitat Kathiresan S, Melander O, Anevski D et al. Polymorphisms associated with cholesterol and risk of cardiovascular events. N Engl J Med. 2008;358:1240–9.PubMed Kathiresan S, Melander O, Anevski D et al. Polymorphisms associated with cholesterol and risk of cardiovascular events. N Engl J Med. 2008;358:1240–9.PubMed
10.
Zurück zum Zitat Cohen JC, Boerwinkle E, Mosley TH Jr et al. Sequence Variations in PCSK9, Low LDL, and Protection against Coronary Heart Disease. N Engl J Med. 2006;354:1264–72.PubMed Cohen JC, Boerwinkle E, Mosley TH Jr et al. Sequence Variations in PCSK9, Low LDL, and Protection against Coronary Heart Disease. N Engl J Med. 2006;354:1264–72.PubMed
11.
Zurück zum Zitat Goldstein JL, Brown MS. Familial hypercholesterolemia: identification of a defect in the regulation of 3-hydroxy-3-methylglutaryl coenzyme A reductase activity associated with overproduction of cholesterol. Proc Natl Acad Sci. 1973;70:2804–8.PubMedCentralPubMed Goldstein JL, Brown MS. Familial hypercholesterolemia: identification of a defect in the regulation of 3-hydroxy-3-methylglutaryl coenzyme A reductase activity associated with overproduction of cholesterol. Proc Natl Acad Sci. 1973;70:2804–8.PubMedCentralPubMed
12.
Zurück zum Zitat Klose G, Laufs U, März W et al. Familiäre Hypercholesterinämie: Entwicklungen in Diagnostik und Behandlung. Dtsch Arztebl Int. 2014;111:523–9.PubMedCentralPubMed Klose G, Laufs U, März W et al. Familiäre Hypercholesterinämie: Entwicklungen in Diagnostik und Behandlung. Dtsch Arztebl Int. 2014;111:523–9.PubMedCentralPubMed
13.
Zurück zum Zitat Baigent C, Blackwell L, Emberson J et al. Efficacy and safety of more intensive lowering of LDL cholesterol: a meta-analysis of data from 170,000 participants in 26 randomised trials. Lancet. 2010;376:1670–81.PubMed Baigent C, Blackwell L, Emberson J et al. Efficacy and safety of more intensive lowering of LDL cholesterol: a meta-analysis of data from 170,000 participants in 26 randomised trials. Lancet. 2010;376:1670–81.PubMed
14.
Zurück zum Zitat Reiner Z, Catapano AL, De Backer G et al. ESC/EAS Guidelines for the management of dyslipidaemias: the Task Force for the management of dyslipidaemias of the European Society of Cardiology (ESC) and the European Atherosclerosis Society (EAS) Eur Heart J. 2011;32:1769–818.PubMed Reiner Z, Catapano AL, De Backer G et al. ESC/EAS Guidelines for the management of dyslipidaemias: the Task Force for the management of dyslipidaemias of the European Society of Cardiology (ESC) and the European Atherosclerosis Society (EAS) Eur Heart J. 2011;32:1769–818.PubMed
15.
Zurück zum Zitat Stone NJ, Robinson JG, Lichtenstein AH et al. 2013 ACC/AHA guideline on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular risk in adults: a report of the American College of Cardiology/ American Heart Association Task Force on Practice Guidelines. Circulation. 2014;129(25 Suppl 2):S1–45.PubMed Stone NJ, Robinson JG, Lichtenstein AH et al. 2013 ACC/AHA guideline on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular risk in adults: a report of the American College of Cardiology/ American Heart Association Task Force on Practice Guidelines. Circulation. 2014;129(25 Suppl 2):S1–45.PubMed
16.
Zurück zum Zitat Boekholdt SM, Hovingh GK, Mora S et al. Very low levels of atherogenic lipoproteins and the risk for cardiovascular events: a meta-analysis of statin trials. J Am Coll Cardiol. 2014;64:485–94.PubMed Boekholdt SM, Hovingh GK, Mora S et al. Very low levels of atherogenic lipoproteins and the risk for cardiovascular events: a meta-analysis of statin trials. J Am Coll Cardiol. 2014;64:485–94.PubMed
17.
Zurück zum Zitat Nicholls SJ, Ballantyne CM, Barter P et al. Effect of Two Intensive Statin Regimens on Progression of Coronary Disease. N Engl J Med. 2011;365:2078–87.PubMed Nicholls SJ, Ballantyne CM, Barter P et al. Effect of Two Intensive Statin Regimens on Progression of Coronary Disease. N Engl J Med. 2011;365:2078–87.PubMed
18.
Zurück zum Zitat Pijlman AH, Huijgen R, Verhagen SN et al. Evaluation of cholesterol lowering treatment of patients with familial hypercholesterolemia: a large cross-sectional study in The Netherlands. Atherosclerosis. 2010;209:189–94.PubMed Pijlman AH, Huijgen R, Verhagen SN et al. Evaluation of cholesterol lowering treatment of patients with familial hypercholesterolemia: a large cross-sectional study in The Netherlands. Atherosclerosis. 2010;209:189–94.PubMed
19.
Zurück zum Zitat Béliard S, Carreau V, Carrié A et al. Improvement in LDL-cholesterol levels of patients with familial hypercholesterolemia: Can we do better? Analysis of results obtained during the past two decades in 1669 French subjects. Atherosclerosis. 2014;234:136–41.PubMed Béliard S, Carreau V, Carrié A et al. Improvement in LDL-cholesterol levels of patients with familial hypercholesterolemia: Can we do better? Analysis of results obtained during the past two decades in 1669 French subjects. Atherosclerosis. 2014;234:136–41.PubMed
20.
Zurück zum Zitat Grundy SM. Statin discontinuation and intolerance: the challenge of lifelong therapy. Ann Intern Med. 2013;158:562–3.PubMed Grundy SM. Statin discontinuation and intolerance: the challenge of lifelong therapy. Ann Intern Med. 2013;158:562–3.PubMed
21.
Zurück zum Zitat Erqou S, Kaptoge S, Perry PL et al. Lipoprotein(a) concentration and the risk of coronary heart disease, stroke, and nonvascular mortality. JAMA. 2009;302:412–23.PubMed Erqou S, Kaptoge S, Perry PL et al. Lipoprotein(a) concentration and the risk of coronary heart disease, stroke, and nonvascular mortality. JAMA. 2009;302:412–23.PubMed
22.
Zurück zum Zitat Kamstrup PR, Tybjaerg-Hansen A, Steffensen R et al. Genetically elevated lipoprotein(a) and increased risk of myocardial infarction. JAMA. 2009;301:2331–9.PubMed Kamstrup PR, Tybjaerg-Hansen A, Steffensen R et al. Genetically elevated lipoprotein(a) and increased risk of myocardial infarction. JAMA. 2009;301:2331–9.PubMed
23.
Zurück zum Zitat Fischer S, Julius U, Tselmin S et al. [Lipoprotein(a): a risk factor for atherosclerosis]. Dtsch Med Wochenschr. 2014;139:1204–6.PubMed Fischer S, Julius U, Tselmin S et al. [Lipoprotein(a): a risk factor for atherosclerosis]. Dtsch Med Wochenschr. 2014;139:1204–6.PubMed
24.
Zurück zum Zitat Nordestgaard BG, Chapman MJ, Ray K et al. Lipoprotein(a) as a cardiovascular risk factor: current status. Eur Heart J. 2010;31:2844–53PubMedCentralPubMed Nordestgaard BG, Chapman MJ, Ray K et al. Lipoprotein(a) as a cardiovascular risk factor: current status. Eur Heart J. 2010;31:2844–53PubMedCentralPubMed
25.
Zurück zum Zitat Leebmann J, Roeseler E, Julius U et al. Lipoprotein Apheresis in Patients With Maximally Tolerated Lipid-Lowering Therapy, Lipoprotein(a)- Hyperlipoproteinemia, and Progressive Cardiovascular Disease: Prospective Observational Multicenter Study. Circulation. 2013;128:2567–76.PubMed Leebmann J, Roeseler E, Julius U et al. Lipoprotein Apheresis in Patients With Maximally Tolerated Lipid-Lowering Therapy, Lipoprotein(a)- Hyperlipoproteinemia, and Progressive Cardiovascular Disease: Prospective Observational Multicenter Study. Circulation. 2013;128:2567–76.PubMed
26.
Zurück zum Zitat Strom TB, Tveten K, Leren TP. PCSK9 acts as a chaperone for the LDL receptor in the endoplasmic reticulum. Biochem J 2014;457:99–105.PubMed Strom TB, Tveten K, Leren TP. PCSK9 acts as a chaperone for the LDL receptor in the endoplasmic reticulum. Biochem J 2014;457:99–105.PubMed
27.
Zurück zum Zitat Grozdanov PN, Petkov PM, Karagyozov LK, Dabeva MD. Expression and localization of PCSK9 in rat hepatic cells. Biochem Cell Biol 2006;84:80–92.PubMed Grozdanov PN, Petkov PM, Karagyozov LK, Dabeva MD. Expression and localization of PCSK9 in rat hepatic cells. Biochem Cell Biol 2006;84:80–92.PubMed
28.
Zurück zum Zitat Benjannet S, Rhainds D, Hamelin J, et al. The proprotein convertase (PC) PCSK9 is inactivated by furin and/or PC5/6A: functional consequences of natural mutations and post-translational modifications. J Biol Chem 2006;281:30561–72.PubMed Benjannet S, Rhainds D, Hamelin J, et al. The proprotein convertase (PC) PCSK9 is inactivated by furin and/or PC5/6A: functional consequences of natural mutations and post-translational modifications. J Biol Chem 2006;281:30561–72.PubMed
29.
Zurück zum Zitat Cameron J, Holla OL, Laerdahl JK, et al. Mutation S462P in the PCSK9 gene reduces secretion of mutant PCSK9 without affecting the autocatalytic cleavage. Atherosclerosis 2009;203:161–5.PubMed Cameron J, Holla OL, Laerdahl JK, et al. Mutation S462P in the PCSK9 gene reduces secretion of mutant PCSK9 without affecting the autocatalytic cleavage. Atherosclerosis 2009;203:161–5.PubMed
30.
Zurück zum Zitat Gustafsen C, Kjolby M, Nyegaard M, et al. The hypercholesterolemiarisk gene SORT1 facilitates PCSK9 secretion. Cell Metab 2014;19:310–8.PubMed Gustafsen C, Kjolby M, Nyegaard M, et al. The hypercholesterolemiarisk gene SORT1 facilitates PCSK9 secretion. Cell Metab 2014;19:310–8.PubMed
31.
Zurück zum Zitat Homer VM, Marais AD, Charlton F, et al. Identification and characterization of two non-secreted PCSK9 mutants associated with familial hypercholesterolemia in cohorts from New Zealand and South Africa. Atherosclerosis 2008;196:659–66.PubMed Homer VM, Marais AD, Charlton F, et al. Identification and characterization of two non-secreted PCSK9 mutants associated with familial hypercholesterolemia in cohorts from New Zealand and South Africa. Atherosclerosis 2008;196:659–66.PubMed
32.
Zurück zum Zitat Chorba JS, Shokat KM. The Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) Active Site and Cleavage Sequence Differentially Regulate Protein Secretion from Proteolysis. J Biol Chem 2014;289:29030–43.PubMed Chorba JS, Shokat KM. The Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) Active Site and Cleavage Sequence Differentially Regulate Protein Secretion from Proteolysis. J Biol Chem 2014;289:29030–43.PubMed
33.
Zurück zum Zitat Dewpura T, Raymond A, Hamelin J, et al. PCSK9 is phosphorylated by a Golgi casein kinase-like kinase ex vivo and circulates as a phosphoprotein in humans. FEBS J 2008;275:3480–93.PubMed Dewpura T, Raymond A, Hamelin J, et al. PCSK9 is phosphorylated by a Golgi casein kinase-like kinase ex vivo and circulates as a phosphoprotein in humans. FEBS J 2008;275:3480–93.PubMed
34.
Zurück zum Zitat Maxwell KN, Breslow JL. Adenoviral-mediated expression of Pcsk9 in mice results in a low-density lipoprotein receptor knockout phenotype. Proc Natl Acad Sci U S A 2004;101:7100–5.PubMedCentralPubMed Maxwell KN, Breslow JL. Adenoviral-mediated expression of Pcsk9 in mice results in a low-density lipoprotein receptor knockout phenotype. Proc Natl Acad Sci U S A 2004;101:7100–5.PubMedCentralPubMed
35.
Zurück zum Zitat Maxwell KN, Fisher EA, Breslow JL. Overexpression of PCSK9 accelerates the degradation of the LDLR in a post-endoplasmic reticulum compartment. Proc Natl Acad Sci U S A 2005;102:2069–74.PubMedCentralPubMed Maxwell KN, Fisher EA, Breslow JL. Overexpression of PCSK9 accelerates the degradation of the LDLR in a post-endoplasmic reticulum compartment. Proc Natl Acad Sci U S A 2005;102:2069–74.PubMedCentralPubMed
36.
Zurück zum Zitat Benjannet S, Rhainds D, Essalmani R, et al. NARC-1/PCSK9 and its natural mutants: zymogen cleavage and effects on the low density lipoprotein (LDL) receptor and LDL cholesterol. J Biol Chem 2004;279:48865–75.PubMed Benjannet S, Rhainds D, Essalmani R, et al. NARC-1/PCSK9 and its natural mutants: zymogen cleavage and effects on the low density lipoprotein (LDL) receptor and LDL cholesterol. J Biol Chem 2004;279:48865–75.PubMed
37.
Zurück zum Zitat Benjannet S, Hamelin J, Chretien M, Seidah NG. Loss- and gain-of-function PCSK9 variants: cleavage specificity, dominant negative effects, and low density lipoprotein receptor (LDLR) degradation. J Biol Chem 2012;287:33745–55.PubMedCentralPubMed Benjannet S, Hamelin J, Chretien M, Seidah NG. Loss- and gain-of-function PCSK9 variants: cleavage specificity, dominant negative effects, and low density lipoprotein receptor (LDLR) degradation. J Biol Chem 2012;287:33745–55.PubMedCentralPubMed
38.
Zurück zum Zitat Chen Y, Wang H, Yu L, et al. Role of ubiquitination in PCSK9-mediated low-density lipoprotein receptor degradation. Biochem Biophys Res Commun 2011;415:515–8.PubMed Chen Y, Wang H, Yu L, et al. Role of ubiquitination in PCSK9-mediated low-density lipoprotein receptor degradation. Biochem Biophys Res Commun 2011;415:515–8.PubMed
39.
Zurück zum Zitat Bottomley MJ, Cirillo A, Orsatti L, et al. Structural and biochemical characterization of the wild type PCSK9-EGF(AB) complex and natural familial hypercholesterolemia mutants. J Biol Chem 2009;284:1313–23.PubMed Bottomley MJ, Cirillo A, Orsatti L, et al. Structural and biochemical characterization of the wild type PCSK9-EGF(AB) complex and natural familial hypercholesterolemia mutants. J Biol Chem 2009;284:1313–23.PubMed
40.
Zurück zum Zitat Zhang DW, Lagace TA, Garuti R, et al. Binding of proprotein convertase subtilisin/kexin type 9 to epidermal growth factor-like repeat A of low density lipoprotein receptor decreases receptor recycling and increases degradation. J Biol Chem 2007;282:18602–12.PubMed Zhang DW, Lagace TA, Garuti R, et al. Binding of proprotein convertase subtilisin/kexin type 9 to epidermal growth factor-like repeat A of low density lipoprotein receptor decreases receptor recycling and increases degradation. J Biol Chem 2007;282:18602–12.PubMed
41.
Zurück zum Zitat Li J, Tumanut C, Gavigan JA, Huang WJ, et al. Secreted PCSK9 promotes LDL receptor degradation independently of proteolytic activity. Biochem J 2007;406:203–7.PubMedCentralPubMed Li J, Tumanut C, Gavigan JA, Huang WJ, et al. Secreted PCSK9 promotes LDL receptor degradation independently of proteolytic activity. Biochem J 2007;406:203–7.PubMedCentralPubMed
42.
Zurück zum Zitat McNutt MC, Lagace TA, Horton JD. Catalytic activity is not required for secreted PCSK9 to reduce low density lipoprotein receptors in HepG2 cells. J Biol Chem 2007;282:20799–803.PubMed McNutt MC, Lagace TA, Horton JD. Catalytic activity is not required for secreted PCSK9 to reduce low density lipoprotein receptors in HepG2 cells. J Biol Chem 2007;282:20799–803.PubMed
43.
Zurück zum Zitat Park SW, Moon YA, Horton JD. Post-transcriptional regulation of low density lipoprotein receptor protein by proprotein convertase subtilisin/ kexin type 9a in mouse liver. J Biol Chem 2004;279:50630–8.PubMed Park SW, Moon YA, Horton JD. Post-transcriptional regulation of low density lipoprotein receptor protein by proprotein convertase subtilisin/ kexin type 9a in mouse liver. J Biol Chem 2004;279:50630–8.PubMed
44.
Zurück zum Zitat Qian YW, Schmidt RJ, Zhang Y, et al. Secreted PCSK9 downregulates low density lipoprotein receptor through receptor-mediated endocytosis. J Lipid Res 2007;48:1488–98.PubMed Qian YW, Schmidt RJ, Zhang Y, et al. Secreted PCSK9 downregulates low density lipoprotein receptor through receptor-mediated endocytosis. J Lipid Res 2007;48:1488–98.PubMed
45.
Zurück zum Zitat Wang Y, Huang Y, Hobbs HH, Cohen JC. Molecular characterization of proprotein convertase subtilisin/kexin type 9-mediated degradation of the LDLR. J Lipid Res 2012;53:1932–43.PubMedCentralPubMed Wang Y, Huang Y, Hobbs HH, Cohen JC. Molecular characterization of proprotein convertase subtilisin/kexin type 9-mediated degradation of the LDLR. J Lipid Res 2012;53:1932–43.PubMedCentralPubMed
46.
Zurück zum Zitat Du F, Hui Y, Zhang M, Linton MF, et al. Novel domain interaction regulates secretion of proprotein convertase subtilisin/kexin type 9 (PCSK9) protein. J Biol Chem 2011;286:43054–61.PubMedCentralPubMed Du F, Hui Y, Zhang M, Linton MF, et al. Novel domain interaction regulates secretion of proprotein convertase subtilisin/kexin type 9 (PCSK9) protein. J Biol Chem 2011;286:43054–61.PubMedCentralPubMed
47.
Zurück zum Zitat Saavedra YG, Day R, Seidah NG. The M2 module of the Cys-His-rich domain (CHRD) of PCSK9 protein is needed for the extracellular low-density lipoprotein receptor (LDLR) degradation pathway. J Biol Chem 2012;287:43492–501.PubMed Saavedra YG, Day R, Seidah NG. The M2 module of the Cys-His-rich domain (CHRD) of PCSK9 protein is needed for the extracellular low-density lipoprotein receptor (LDLR) degradation pathway. J Biol Chem 2012;287:43492–501.PubMed
48.
Zurück zum Zitat Leren TP. Mutations in the PCSK9 gene in Norwegian subjects with autosomal dominant hypercholesterolemia. Clin Genet 2004;65:419–22.PubMed Leren TP. Mutations in the PCSK9 gene in Norwegian subjects with autosomal dominant hypercholesterolemia. Clin Genet 2004;65:419–22.PubMed
49.
Zurück zum Zitat Fan D, Yancey PG, Qiu S, et al. Self-association of human PCSK9 correlates with its LDLR-degrading activity. Biochemistry 2008;47:1631–9.PubMedCentralPubMed Fan D, Yancey PG, Qiu S, et al. Self-association of human PCSK9 correlates with its LDLR-degrading activity. Biochemistry 2008;47:1631–9.PubMedCentralPubMed
50.
Zurück zum Zitat Tavori H, Fan D, Blakemore JL, et al. Serum proprotein convertase subtilisin/ kexin type 9 and cell surface low-density lipoprotein receptor: evidence for a reciprocal regulation. Circulation 2013;127:2403–13.PubMedCentralPubMed Tavori H, Fan D, Blakemore JL, et al. Serum proprotein convertase subtilisin/ kexin type 9 and cell surface low-density lipoprotein receptor: evidence for a reciprocal regulation. Circulation 2013;127:2403–13.PubMedCentralPubMed
51.
Zurück zum Zitat Cameron J, Bogsrud MP, Tveten K, et al. Serum levels of proprotein convertase subtilisin/kexin type 9 in subjects with familial hypercholesterolemia indicate that proprotein convertase subtilisin/kexin type 9 is cleared from plasma by low-density lipoprotein receptor-independent pathways. Transl Res 2012;160:125–30.PubMed Cameron J, Bogsrud MP, Tveten K, et al. Serum levels of proprotein convertase subtilisin/kexin type 9 in subjects with familial hypercholesterolemia indicate that proprotein convertase subtilisin/kexin type 9 is cleared from plasma by low-density lipoprotein receptor-independent pathways. Transl Res 2012;160:125–30.PubMed
52.
Zurück zum Zitat Kosenko T, Golder M, Leblond G, et al. Low density lipoprotein binds to proprotein convertase subtilisin/kexin type-9 (PCSK9) in human plasma and inhibits PCSK9-mediated low density lipoprotein receptor degradation. J Biol Chem 2013;288:8279–88.PubMedCentralPubMed Kosenko T, Golder M, Leblond G, et al. Low density lipoprotein binds to proprotein convertase subtilisin/kexin type-9 (PCSK9) in human plasma and inhibits PCSK9-mediated low density lipoprotein receptor degradation. J Biol Chem 2013;288:8279–88.PubMedCentralPubMed
53.
Zurück zum Zitat Essalmani R, Susan-Resiga D, Chamberland A, et al. In vivo evidence that furin from hepatocytes inactivates PCSK9. J Biol Chem 2011;286:4257–63.PubMedCentralPubMed Essalmani R, Susan-Resiga D, Chamberland A, et al. In vivo evidence that furin from hepatocytes inactivates PCSK9. J Biol Chem 2011;286:4257–63.PubMedCentralPubMed
54.
Zurück zum Zitat Han B, Eacho PI, Knierman MD, et al. Isolation and characterization of the circulating truncated form of PCSK9. J Lipid Res 2014;55:1505–14.PubMed Han B, Eacho PI, Knierman MD, et al. Isolation and characterization of the circulating truncated form of PCSK9. J Lipid Res 2014;55:1505–14.PubMed
55.
Zurück zum Zitat Lipari MT, Li W, Moran P, et al. Furin-cleaved proprotein convertase subtilisin/kexin type 9 (PCSK9) is active and modulates low density lipoprotein receptor and serum cholesterol levels. J Biol Chem 2012;287:43482–91.PubMedCentralPubMed Lipari MT, Li W, Moran P, et al. Furin-cleaved proprotein convertase subtilisin/kexin type 9 (PCSK9) is active and modulates low density lipoprotein receptor and serum cholesterol levels. J Biol Chem 2012;287:43482–91.PubMedCentralPubMed
56.
Zurück zum Zitat Xu W, Liu L, Hornby D. c-IAP1 binds and processes PCSK9 protein: linking the c-IAP1 in a TNF-alpha pathway to PCSK9-mediated LDLR degradation pathway. Molecules 2012;17:12086–101.PubMed Xu W, Liu L, Hornby D. c-IAP1 binds and processes PCSK9 protein: linking the c-IAP1 in a TNF-alpha pathway to PCSK9-mediated LDLR degradation pathway. Molecules 2012;17:12086–101.PubMed
57.
Zurück zum Zitat Seidah NG, Poirier S, Denis M, et al. Annexin A2 is a natural extrahepatic inhibitor of the PCSK9-induced LDL receptor degradation. PLoS One 2012;7:e41865.PubMedCentralPubMed Seidah NG, Poirier S, Denis M, et al. Annexin A2 is a natural extrahepatic inhibitor of the PCSK9-induced LDL receptor degradation. PLoS One 2012;7:e41865.PubMedCentralPubMed
58.
Zurück zum Zitat Mayer G, Poirier S, Seidah NG. Annexin A2 is a C-terminal PCSK9-binding protein that regulates endogenous low density lipoprotein receptor levels. J Biol Chem 2008;283:31791–801.PubMed Mayer G, Poirier S, Seidah NG. Annexin A2 is a C-terminal PCSK9-binding protein that regulates endogenous low density lipoprotein receptor levels. J Biol Chem 2008;283:31791–801.PubMed
59.
Zurück zum Zitat Cariou B, Langhi C, Le BM, et al. Plasma PCSK9 concentrations during an oral fat load and after short term high-fat, high-fat high-protein and high-fructose diets. Nutr Metab (Lond) 2013;10:4. Cariou B, Langhi C, Le BM, et al. Plasma PCSK9 concentrations during an oral fat load and after short term high-fat, high-fat high-protein and high-fructose diets. Nutr Metab (Lond) 2013;10:4.
60.
Zurück zum Zitat Persson L, Cao G, Stahle L, et al. Circulating proprotein convertase subtilisin kexin type 9 has a diurnal rhythm synchronous with cholesterol synthesis and is reduced by fasting in humans. Arterioscler Thromb Vasc Biol 2010;30:2666–72.PubMed Persson L, Cao G, Stahle L, et al. Circulating proprotein convertase subtilisin kexin type 9 has a diurnal rhythm synchronous with cholesterol synthesis and is reduced by fasting in humans. Arterioscler Thromb Vasc Biol 2010;30:2666–72.PubMed
61.
Zurück zum Zitat Lakoski SG, Lagace TA, Cohen JC, et al. Genetic and metabolic determinants of plasma PCSK9 levels. J Clin Endocrinol Metab 2009;94:2537–43.PubMedCentralPubMed Lakoski SG, Lagace TA, Cohen JC, et al. Genetic and metabolic determinants of plasma PCSK9 levels. J Clin Endocrinol Metab 2009;94:2537–43.PubMedCentralPubMed
62.
Zurück zum Zitat Baass A, Dubuc G, Tremblay M, et al. Plasma PCSK9 is associated with age, sex, and multiple metabolic markers in a population-based sample of children and adolescents. Clin Chem 2009;55:1637–45.PubMed Baass A, Dubuc G, Tremblay M, et al. Plasma PCSK9 is associated with age, sex, and multiple metabolic markers in a population-based sample of children and adolescents. Clin Chem 2009;55:1637–45.PubMed
63.
Zurück zum Zitat Persson L, Henriksson P, Westerlund E, et al. Endogenous estrogens lower plasma PCSK9 and LDL cholesterol but not Lp(a) or bile acid synthesis in women. Arterioscler Thromb Vasc Biol 2012;32:810–4.PubMed Persson L, Henriksson P, Westerlund E, et al. Endogenous estrogens lower plasma PCSK9 and LDL cholesterol but not Lp(a) or bile acid synthesis in women. Arterioscler Thromb Vasc Biol 2012;32:810–4.PubMed
64.
Zurück zum Zitat Chernogubova E, Strawbridge R, Mahdessian H, et al. Common and low-frequency genetic variants in the PCSK9 locus influence circulating PCSK9 levels. Arterioscler Thromb Vasc Biol 2012;32:1526–34.PubMed Chernogubova E, Strawbridge R, Mahdessian H, et al. Common and low-frequency genetic variants in the PCSK9 locus influence circulating PCSK9 levels. Arterioscler Thromb Vasc Biol 2012;32:1526–34.PubMed
65.
Zurück zum Zitat Alborn WE, Cao G, Careskey HE, et al. Serum proprotein convertase subtilisin kexin type 9 is correlated directly with serum LDL cholesterol. Clin Chem 2007;53:1814–9.PubMed Alborn WE, Cao G, Careskey HE, et al. Serum proprotein convertase subtilisin kexin type 9 is correlated directly with serum LDL cholesterol. Clin Chem 2007;53:1814–9.PubMed
66.
Zurück zum Zitat Araki S, Suga S, Miyake F, et al. Circulating PCSK9 levels correlate with the serum LDL cholesterol level in newborn infants. Early Hum Dev 2014;90:607–11.PubMed Araki S, Suga S, Miyake F, et al. Circulating PCSK9 levels correlate with the serum LDL cholesterol level in newborn infants. Early Hum Dev 2014;90:607–11.PubMed
67.
Zurück zum Zitat Lambert G, Petrides F, Chatelais M, et al. Elevated Plasma PCSK9 Level Is Equally Detrimental for Patients With Nonfamilial Hypercholesterolemia and Heterozygous Familial Hypercholesterolemia, Irrespective of Low-Density Lipoprotein Receptor Defects. J Am Coll Cardiol 2014;63:2365–73.PubMed Lambert G, Petrides F, Chatelais M, et al. Elevated Plasma PCSK9 Level Is Equally Detrimental for Patients With Nonfamilial Hypercholesterolemia and Heterozygous Familial Hypercholesterolemia, Irrespective of Low-Density Lipoprotein Receptor Defects. J Am Coll Cardiol 2014;63:2365–73.PubMed
68.
Zurück zum Zitat Brouwers MC, Troutt JS, van Greevenbroek MM, et al. Plasma proprotein convertase subtilisin kexin type 9 is not altered in subjects with impaired glucose metabolism and type 2 diabetes mellitus, but its relationship with non-HDL cholesterol and apolipoprotein B may be modified by type 2 diabetes mellitus: The CODAM study. Atherosclerosis 2011;217:263–7.PubMed Brouwers MC, Troutt JS, van Greevenbroek MM, et al. Plasma proprotein convertase subtilisin kexin type 9 is not altered in subjects with impaired glucose metabolism and type 2 diabetes mellitus, but its relationship with non-HDL cholesterol and apolipoprotein B may be modified by type 2 diabetes mellitus: The CODAM study. Atherosclerosis 2011;217:263–7.PubMed
69.
Zurück zum Zitat Tavori H, Giunzioni I, Linton MF, Fazio S. Loss of plasma proprotein convertase subtilisin/kexin 9 (PCSK9) after lipoprotein apheresis. Circ Res 2013;113:1290–5.PubMedCentralPubMed Tavori H, Giunzioni I, Linton MF, Fazio S. Loss of plasma proprotein convertase subtilisin/kexin 9 (PCSK9) after lipoprotein apheresis. Circ Res 2013;113:1290–5.PubMedCentralPubMed
70.
Zurück zum Zitat Hori M, Ishihara M, Yuasa Y, et al. Removal of plasma mature and furincleaved proprotein convertase subtilisin/kexin 9 (PCSK9) by low-density lipoprotein-apheresis in familial hypercholesterolemia: development and application of a new assay for PCSK9. J Clin Endocrinol Metab 2014:jc20143066. Hori M, Ishihara M, Yuasa Y, et al. Removal of plasma mature and furincleaved proprotein convertase subtilisin/kexin 9 (PCSK9) by low-density lipoprotein-apheresis in familial hypercholesterolemia: development and application of a new assay for PCSK9. J Clin Endocrinol Metab 2014:jc20143066.
71.
Zurück zum Zitat Wu M, Dong B, Cao A, Li H, Liu J. Delineation of molecular pathways that regulate hepatic PCSK9 and LDL receptor expression during fasting in normolipidemic hamsters. Atherosclerosis 2012;224:401–10.PubMed Wu M, Dong B, Cao A, Li H, Liu J. Delineation of molecular pathways that regulate hepatic PCSK9 and LDL receptor expression during fasting in normolipidemic hamsters. Atherosclerosis 2012;224:401–10.PubMed
72.
Zurück zum Zitat Browning JD, Horton JD. Fasting reduces plasma proprotein convertase, subtilisin/kexin type 9 and cholesterol biosynthesis in humans. J Lipid Res 2010;51:3359–63.PubMedCentralPubMed Browning JD, Horton JD. Fasting reduces plasma proprotein convertase, subtilisin/kexin type 9 and cholesterol biosynthesis in humans. J Lipid Res 2010;51:3359–63.PubMedCentralPubMed
73.
Zurück zum Zitat Costet P, Cariou B, Lambert G, et al. Hepatic PCSK9 expression is regulated by nutritional status via insulin and sterol regulatory elementbinding protein 1c. J Biol Chem 2006;281:6211–8.PubMed Costet P, Cariou B, Lambert G, et al. Hepatic PCSK9 expression is regulated by nutritional status via insulin and sterol regulatory elementbinding protein 1c. J Biol Chem 2006;281:6211–8.PubMed
74.
Zurück zum Zitat Ai D, Chen C, Han S, Ganda A, et al. Regulation of hepatic LDL receptors by mTORC1 and PCSK9 in mice. J Clin Invest 2012;122:1262–70.PubMedCentralPubMed Ai D, Chen C, Han S, Ganda A, et al. Regulation of hepatic LDL receptors by mTORC1 and PCSK9 in mice. J Clin Invest 2012;122:1262–70.PubMedCentralPubMed
75.
Zurück zum Zitat Awan Z, Dubuc G, Faraj M, et al. The effect of insulin on circulating PCSK9 in postmenopausal obese women. Clin Biochem 2014. Awan Z, Dubuc G, Faraj M, et al. The effect of insulin on circulating PCSK9 in postmenopausal obese women. Clin Biochem 2014.
76.
Zurück zum Zitat Kappelle PJ, Lambert G, Dullaart RP. Plasma proprotein convertase subtilisin-kexin type 9 does not change during 24h insulin infusion in healthy subjects and type 2 diabetic patients. Atherosclerosis 2011;214:432–5.PubMed Kappelle PJ, Lambert G, Dullaart RP. Plasma proprotein convertase subtilisin-kexin type 9 does not change during 24h insulin infusion in healthy subjects and type 2 diabetic patients. Atherosclerosis 2011;214:432–5.PubMed
77.
Zurück zum Zitat Kourimate S, Le MC, Langhi C, et al. Dual mechanisms for the fibratemediated repression of proprotein convertase subtilisin/kexin type 9. J Biol Chem 2008;283:9666–73.PubMed Kourimate S, Le MC, Langhi C, et al. Dual mechanisms for the fibratemediated repression of proprotein convertase subtilisin/kexin type 9. J Biol Chem 2008;283:9666–73.PubMed
78.
Zurück zum Zitat Duan Y, Chen Y, Hu W, et al. Peroxisome Proliferator-activated receptor gamma activation by ligands and dephosphorylation induces proprotein convertase subtilisin kexin type 9 and low density lipoprotein receptor expression. J Biol Chem 2012;287:23667–77.PubMedCentralPubMed Duan Y, Chen Y, Hu W, et al. Peroxisome Proliferator-activated receptor gamma activation by ligands and dephosphorylation induces proprotein convertase subtilisin kexin type 9 and low density lipoprotein receptor expression. J Biol Chem 2012;287:23667–77.PubMedCentralPubMed
79.
Zurück zum Zitat Langhi C, Le MC, Kourimate S, et al. Activation of the farnesoid X receptor represses PCSK9 expression in human hepatocytes. FEBS Lett 2008;582:949–55.PubMed Langhi C, Le MC, Kourimate S, et al. Activation of the farnesoid X receptor represses PCSK9 expression in human hepatocytes. FEBS Lett 2008;582:949–55.PubMed
80.
Zurück zum Zitat Scotti E, Hong C, Yoshinaga Y, et al. Targeted disruption of the idol gene alters cellular regulation of the low-density lipoprotein receptor by sterols and liver x receptor agonists. Mol Cell Biol 2011;31:1885–93.PubMedCentralPubMed Scotti E, Hong C, Yoshinaga Y, et al. Targeted disruption of the idol gene alters cellular regulation of the low-density lipoprotein receptor by sterols and liver x receptor agonists. Mol Cell Biol 2011;31:1885–93.PubMedCentralPubMed
81.
Zurück zum Zitat Li H, Liu J. The novel function of HINFP as a co-activator in sterol-regulated transcription of PCSK9 in HepG2 cells. Biochem J 2012;443:757–68.PubMed Li H, Liu J. The novel function of HINFP as a co-activator in sterol-regulated transcription of PCSK9 in HepG2 cells. Biochem J 2012;443:757–68.PubMed
82.
Zurück zum Zitat Tao R, Xiong X, DePinho RA, et al. FoxO3 transcription factor and Sirt6 deacetylase regulate low density lipoprotein (LDL)-cholesterol homeostasis via control of the proprotein convertase subtilisin/kexin type 9 (Pcsk9) gene expression. J Biol Chem 2013;288:29252–9.PubMedCentralPubMed Tao R, Xiong X, DePinho RA, et al. FoxO3 transcription factor and Sirt6 deacetylase regulate low density lipoprotein (LDL)-cholesterol homeostasis via control of the proprotein convertase subtilisin/kexin type 9 (Pcsk9) gene expression. J Biol Chem 2013;288:29252–9.PubMedCentralPubMed
83.
Zurück zum Zitat Miranda MX, van Tits LJ, Lohmann C, et al. The Sirt1 activator SRT3025 provides atheroprotection in Apoe-/- mice by reducing hepatic Pcsk9 secretion and enhancing Ldlr expression. Eur Heart J 2014. Miranda MX, van Tits LJ, Lohmann C, et al. The Sirt1 activator SRT3025 provides atheroprotection in Apoe-/- mice by reducing hepatic Pcsk9 secretion and enhancing Ldlr expression. Eur Heart J 2014.
84.
Zurück zum Zitat Melone M, Wilsie L, Palyha O, et al. Discovery of a new role of human resistin in hepatocyte low-density lipoprotein receptor suppression mediated in part by proprotein convertase subtilisin/kexin type 9. J Am Coll Cardiol 2012;59:1697–705.PubMed Melone M, Wilsie L, Palyha O, et al. Discovery of a new role of human resistin in hepatocyte low-density lipoprotein receptor suppression mediated in part by proprotein convertase subtilisin/kexin type 9. J Am Coll Cardiol 2012;59:1697–705.PubMed
85.
Zurück zum Zitat Ason B, Tep S, Davis HR, Jr., et al. Improved efficacy for ezetimibe and rosuvastatin by attenuating the induction of PCSK9. J Lipid Res 2011;52:679–87.PubMedCentralPubMed Ason B, Tep S, Davis HR, Jr., et al. Improved efficacy for ezetimibe and rosuvastatin by attenuating the induction of PCSK9. J Lipid Res 2011;52:679–87.PubMedCentralPubMed
86.
Zurück zum Zitat Berthold HK, Seidah NG, Benjannet S, Gouni-Berthold I. Evidence from a randomized trial that simvastatin, but not ezetimibe, upregulates circulating PCSK9 levels. PLoS One 2013;8:e60095.PubMedCentralPubMed Berthold HK, Seidah NG, Benjannet S, Gouni-Berthold I. Evidence from a randomized trial that simvastatin, but not ezetimibe, upregulates circulating PCSK9 levels. PLoS One 2013;8:e60095.PubMedCentralPubMed
87.
Zurück zum Zitat Romano M, Di Taranto MD, D‘Agostino MN, et al. Identification and functional characterization of LDLR mutations in familial hypercholesterolemia patients from Southern Italy. Atherosclerosis 2010;210:493–6.PubMed Romano M, Di Taranto MD, D‘Agostino MN, et al. Identification and functional characterization of LDLR mutations in familial hypercholesterolemia patients from Southern Italy. Atherosclerosis 2010;210:493–6.PubMed
88.
Zurück zum Zitat Guo YL, Liu J, Xu RX, et al. Short-term impact of low-dose atorvastatin on serum proprotein convertase subtilisin/kexin type 9. Clin Drug Investig 2013;33:877–83.PubMed Guo YL, Liu J, Xu RX, et al. Short-term impact of low-dose atorvastatin on serum proprotein convertase subtilisin/kexin type 9. Clin Drug Investig 2013;33:877–83.PubMed
89.
Zurück zum Zitat Noguchi T, Kobayashi J, Yagi K, et al. Comparison of effects of bezafibrate and fenofibrate on circulating proprotein convertase subtilisin/ kexin type 9 and adipocytokine levels in dyslipidemic subjects with impaired glucose tolerance or type 2 diabetes mellitus: results from a crossover study. Atherosclerosis 2011;217:165–70.PubMed Noguchi T, Kobayashi J, Yagi K, et al. Comparison of effects of bezafibrate and fenofibrate on circulating proprotein convertase subtilisin/ kexin type 9 and adipocytokine levels in dyslipidemic subjects with impaired glucose tolerance or type 2 diabetes mellitus: results from a crossover study. Atherosclerosis 2011;217:165–70.PubMed
90.
Zurück zum Zitat Costet P, Hoffmann MM, Cariou B, et al. Plasma PCSK9 is increased by fenofibrate and atorvastatin in a non-additive fashion in diabetic patients. Atherosclerosis 2010;212:246–51.PubMed Costet P, Hoffmann MM, Cariou B, et al. Plasma PCSK9 is increased by fenofibrate and atorvastatin in a non-additive fashion in diabetic patients. Atherosclerosis 2010;212:246–51.PubMed
91.
Zurück zum Zitat Cariou B, Le BM, Langhi C, et al. Association between plasma PCSK9 and gamma-glutamyl transferase levels in diabetic patients. Atherosclerosis 2010;211:700–2.PubMed Cariou B, Le BM, Langhi C, et al. Association between plasma PCSK9 and gamma-glutamyl transferase levels in diabetic patients. Atherosclerosis 2010;211:700–2.PubMed
92.
Zurück zum Zitat Dong B, Wu M, Li H, Kraemer FB, et al. Strong induction of PCSK9 gene expression through HNF1alpha and SREBP2: mechanism for the resistance to LDL-cholesterol lowering effect of statins in dyslipidemic hamsters. J Lipid Res 2010;51:1486–95.PubMedCentralPubMed Dong B, Wu M, Li H, Kraemer FB, et al. Strong induction of PCSK9 gene expression through HNF1alpha and SREBP2: mechanism for the resistance to LDL-cholesterol lowering effect of statins in dyslipidemic hamsters. J Lipid Res 2010;51:1486–95.PubMedCentralPubMed
93.
Zurück zum Zitat Nozue T, Hattori H, Ishihara M, et al. Comparison of effects of pitavastatin versus pravastatin on serum proprotein convertase subtilisin/kexin type 9 levels in statin-naive patients with coronary artery disease. Am J Cardiol 2013;111:1415–9.PubMed Nozue T, Hattori H, Ishihara M, et al. Comparison of effects of pitavastatin versus pravastatin on serum proprotein convertase subtilisin/kexin type 9 levels in statin-naive patients with coronary artery disease. Am J Cardiol 2013;111:1415–9.PubMed
94.
Zurück zum Zitat Awan Z, Seidah NG, MacFadyen JG, et al. Rosuvastatin, proprotein convertase subtilisin/kexin type 9 concentrations, and LDL cholesterol response: the JUPITER trial. Clin Chem 2012;58:183–9.PubMed Awan Z, Seidah NG, MacFadyen JG, et al. Rosuvastatin, proprotein convertase subtilisin/kexin type 9 concentrations, and LDL cholesterol response: the JUPITER trial. Clin Chem 2012;58:183–9.PubMed
95.
Zurück zum Zitat Dubuc G, Chamberland A, Wassef H, et al. Statins upregulate PCSK9, the gene encoding the proprotein convertase neural apoptosis-regulated convertase-1 implicated in familial hypercholesterolemia. Arterioscler Thromb Vasc Biol 2004;24:1454–9.PubMed Dubuc G, Chamberland A, Wassef H, et al. Statins upregulate PCSK9, the gene encoding the proprotein convertase neural apoptosis-regulated convertase-1 implicated in familial hypercholesterolemia. Arterioscler Thromb Vasc Biol 2004;24:1454–9.PubMed
96.
Zurück zum Zitat Mayne J, Dewpura T, Raymond A, et al. Plasma PCSK9 levels are significantly modified by statins and fibrates in humans. Lipids Health Dis 2008;7:22.PubMedCentralPubMed Mayne J, Dewpura T, Raymond A, et al. Plasma PCSK9 levels are significantly modified by statins and fibrates in humans. Lipids Health Dis 2008;7:22.PubMedCentralPubMed
97.
Zurück zum Zitat Lambert G, Ancellin N, Charlton F, et al. Plasma PCSK9 concentrations correlate with LDL and total cholesterol in diabetic patients and are decreased by fenofibrate treatment. Clin Chem 2008;54:1038–45.PubMed Lambert G, Ancellin N, Charlton F, et al. Plasma PCSK9 concentrations correlate with LDL and total cholesterol in diabetic patients and are decreased by fenofibrate treatment. Clin Chem 2008;54:1038–45.PubMed
98.
Zurück zum Zitat Troutt JS, Alborn WE, Cao G, Konrad RJ. Fenofibrate treatment increases human serum proprotein convertase subtilisin kexin type 9 levels. J Lipid Res 2010;51:345–51.PubMedCentralPubMed Troutt JS, Alborn WE, Cao G, Konrad RJ. Fenofibrate treatment increases human serum proprotein convertase subtilisin kexin type 9 levels. J Lipid Res 2010;51:345–51.PubMedCentralPubMed
99.
Zurück zum Zitat Sahebkar A. Circulating Levels of Proprotein Convertase Subtilisin Kexin Type 9 are Elevated by Fibrate Therapy: A Systematic Review and Meta-analysis of Clinical Trials. Cardiol Rev 2014. Sahebkar A. Circulating Levels of Proprotein Convertase Subtilisin Kexin Type 9 are Elevated by Fibrate Therapy: A Systematic Review and Meta-analysis of Clinical Trials. Cardiol Rev 2014.
100.
Zurück zum Zitat Hentze H, Jensen KK, Chia SM, et al. Inverse relationship between LDL cholesterol and PCSK9 plasma levels in dyslipidemic cynomolgus monkeys: effects of LDL lowering by ezetimibe in the absence of statins. Atherosclerosis 2013;231:84–90.PubMed Hentze H, Jensen KK, Chia SM, et al. Inverse relationship between LDL cholesterol and PCSK9 plasma levels in dyslipidemic cynomolgus monkeys: effects of LDL lowering by ezetimibe in the absence of statins. Atherosclerosis 2013;231:84–90.PubMed
101.
Zurück zum Zitat Feingold KR, Moser AH, Shigenaga JK, et al. Inflammation stimulates the expression of PCSK9. Biochem Biophys Res Commun 2008;374:341–4.PubMedCentralPubMed Feingold KR, Moser AH, Shigenaga JK, et al. Inflammation stimulates the expression of PCSK9. Biochem Biophys Res Commun 2008;374:341–4.PubMedCentralPubMed
102.
Zurück zum Zitat Li S, Guo YL, Xu RX, et al. Association of plasma PCSK9 levels with white blood cell count and its subsets in patients with stable coronary artery disease. Atherosclerosis 2014;234:441–5.PubMed Li S, Guo YL, Xu RX, et al. Association of plasma PCSK9 levels with white blood cell count and its subsets in patients with stable coronary artery disease. Atherosclerosis 2014;234:441–5.PubMed
103.
Zurück zum Zitat Zhang Y, Zhu CG, Xu RX, et al. Relation of circulating PCSK9 concentration to fibrinogen in patients with stable coronary artery disease. J Clin Lipidol 2014;8:494–500.PubMed Zhang Y, Zhu CG, Xu RX, et al. Relation of circulating PCSK9 concentration to fibrinogen in patients with stable coronary artery disease. J Clin Lipidol 2014;8:494–500.PubMed
104.
Zurück zum Zitat Almontashiri NA, Vilmundarson RO, Ghasemzadeh N, Dandona S, Roberts R, Quyyumi AA, et al. Plasma PCSK9 Levels Are Elevated with Acute Myocardial Infarction in Two Independent Retrospective Angiographic Studies. PLoS One 2014;9:e106294.PubMedCentralPubMed Almontashiri NA, Vilmundarson RO, Ghasemzadeh N, Dandona S, Roberts R, Quyyumi AA, et al. Plasma PCSK9 Levels Are Elevated with Acute Myocardial Infarction in Two Independent Retrospective Angiographic Studies. PLoS One 2014;9:e106294.PubMedCentralPubMed
105.
Zurück zum Zitat Kwakernaak AJ, Lambert G, Slagman MC, et al. Proprotein convertase subtilisin-kexin type 9 is elevated in proteinuric subjects: relationship with lipoprotein response to antiproteinuric treatment. Atherosclerosis 2013;226:459–65.PubMed Kwakernaak AJ, Lambert G, Slagman MC, et al. Proprotein convertase subtilisin-kexin type 9 is elevated in proteinuric subjects: relationship with lipoprotein response to antiproteinuric treatment. Atherosclerosis 2013;226:459–65.PubMed
106.
Zurück zum Zitat Jin K, Park BS, Kim YW, Vaziri ND. Plasma PCSK9 in nephrotic syndrome and in peritoneal dialysis: a cross-sectional study. Am J Kidney Dis 2014;63:584–9.PubMed Jin K, Park BS, Kim YW, Vaziri ND. Plasma PCSK9 in nephrotic syndrome and in peritoneal dialysis: a cross-sectional study. Am J Kidney Dis 2014;63:584–9.PubMed
107.
Zurück zum Zitat Roche-Molina M, Sanz-Rosa D, Cruz FM, et al. Induction of Sustained Hypercholesterolemia by Single Adeno-Associated Virus-Mediated Gene Transfer of Mutant hPCSK9. Arterioscler Thromb Vasc Biol 2014. Roche-Molina M, Sanz-Rosa D, Cruz FM, et al. Induction of Sustained Hypercholesterolemia by Single Adeno-Associated Virus-Mediated Gene Transfer of Mutant hPCSK9. Arterioscler Thromb Vasc Biol 2014.
108.
Zurück zum Zitat Al-Mashhadi RH, Sorensen CB, Kragh PM, et al. Familial hypercholesterolemia and atherosclerosis in cloned minipigs created by DNA transposition of a human PCSK9 gain-of-function mutant. Sci Transl Med 2013;5:166ra1.PubMed Al-Mashhadi RH, Sorensen CB, Kragh PM, et al. Familial hypercholesterolemia and atherosclerosis in cloned minipigs created by DNA transposition of a human PCSK9 gain-of-function mutant. Sci Transl Med 2013;5:166ra1.PubMed
109.
Zurück zum Zitat Denis M, Marcinkiewicz J, Zaid A, et al. Gene inactivation of proprotein convertase subtilisin/kexin type 9 reduces atherosclerosis in mice. Circulation 2012;125:894–901.PubMed Denis M, Marcinkiewicz J, Zaid A, et al. Gene inactivation of proprotein convertase subtilisin/kexin type 9 reduces atherosclerosis in mice. Circulation 2012;125:894–901.PubMed
110.
Zurück zum Zitat Shen L, Peng HC, Nees SN, et al. Proprotein convertase subtilisin/kexin type 9 potentially influences cholesterol uptake in macrophages and reverse cholesterol transport. FEBS Lett 2013;587:1271–4.PubMed Shen L, Peng HC, Nees SN, et al. Proprotein convertase subtilisin/kexin type 9 potentially influences cholesterol uptake in macrophages and reverse cholesterol transport. FEBS Lett 2013;587:1271–4.PubMed
111.
Zurück zum Zitat Tang Z, Jiang L, Peng J, et al. PCSK9 siRNA suppresses the inflammatory response induced by oxLDL through inhibition of NF-kappaB activation in THP-1-derived macrophages. Int J Mol Med 2012;30:931–8.PubMed Tang Z, Jiang L, Peng J, et al. PCSK9 siRNA suppresses the inflammatory response induced by oxLDL through inhibition of NF-kappaB activation in THP-1-derived macrophages. Int J Mol Med 2012;30:931–8.PubMed
112.
Zurück zum Zitat Wu CY, Tang ZH, Jiang L, et al. PCSK9 siRNA inhibits HUVEC apoptosis induced by ox-LDL via Bcl/Bax-caspase9-caspase3 pathway. Mol Cell Biochem 2012;359:347–58.PubMed Wu CY, Tang ZH, Jiang L, et al. PCSK9 siRNA inhibits HUVEC apoptosis induced by ox-LDL via Bcl/Bax-caspase9-caspase3 pathway. Mol Cell Biochem 2012;359:347–58.PubMed
113.
Zurück zum Zitat Kuhnast S, van der Hoorn JW, Pieterman EJ, et al. Alirocumab inhibits atherosclerosis, improves the plaque morphology, and enhances the effects of a statin. J Lipid Res 2014;55:2103–12.PubMedCentralPubMed Kuhnast S, van der Hoorn JW, Pieterman EJ, et al. Alirocumab inhibits atherosclerosis, improves the plaque morphology, and enhances the effects of a statin. J Lipid Res 2014;55:2103–12.PubMedCentralPubMed
114.
Zurück zum Zitat Ason B, van der Hoorn JW, Chan J, et al. PCSK9 inhibition fails to alter hepatic LDLR, circulating cholesterol, and atherosclerosis in the absence of ApoE. J Lipid Res 2014;55:2370–9.PubMed Ason B, van der Hoorn JW, Chan J, et al. PCSK9 inhibition fails to alter hepatic LDLR, circulating cholesterol, and atherosclerosis in the absence of ApoE. J Lipid Res 2014;55:2370–9.PubMed
115.
Zurück zum Zitat Kysenius K, Muggalla P, Matlik K, et al. PCSK9 regulates neuronal apoptosis by adjusting ApoER2 levels and signaling. Cell Mol Life Sci 2012;69:1903–16.PubMed Kysenius K, Muggalla P, Matlik K, et al. PCSK9 regulates neuronal apoptosis by adjusting ApoER2 levels and signaling. Cell Mol Life Sci 2012;69:1903–16.PubMed
116.
Zurück zum Zitat Poirier S, Mayer G, Benjannet S, et al. The proprotein convertase PCSK9 induces the degradation of low density lipoprotein receptor (LDLR) and its closest family members VLDLR and ApoER2. J Biol Chem 2008;283:2363–72.PubMed Poirier S, Mayer G, Benjannet S, et al. The proprotein convertase PCSK9 induces the degradation of low density lipoprotein receptor (LDLR) and its closest family members VLDLR and ApoER2. J Biol Chem 2008;283:2363–72.PubMed
117.
Zurück zum Zitat Canuel M, Sun X, Asselin MC, et al. Proprotein convertase subtilisin/kexin type 9 (PCSK9) can mediate degradation of the low density lipoprotein receptor-related protein 1 (LRP-1). PLoS One 2013;8:e64145.PubMedCentralPubMed Canuel M, Sun X, Asselin MC, et al. Proprotein convertase subtilisin/kexin type 9 (PCSK9) can mediate degradation of the low density lipoprotein receptor-related protein 1 (LRP-1). PLoS One 2013;8:e64145.PubMedCentralPubMed
118.
Zurück zum Zitat Labonte P, Begley S, Guevin C, et al. PCSK9 impedes hepatitis C virus infection in vitro and modulates liver CD81 expression. Hepatology 2009;50:17–24.PubMed Labonte P, Begley S, Guevin C, et al. PCSK9 impedes hepatitis C virus infection in vitro and modulates liver CD81 expression. Hepatology 2009;50:17–24.PubMed
119.
Zurück zum Zitat Shan L, Pang L, Zhang R, et al. PCSK9 binds to multiple receptors and can be functionally inhibited by an EGF-A peptide. Biochem Biophys Res Commun 2008;375:69–73.PubMed Shan L, Pang L, Zhang R, et al. PCSK9 binds to multiple receptors and can be functionally inhibited by an EGF-A peptide. Biochem Biophys Res Commun 2008;375:69–73.PubMed
120.
Zurück zum Zitat Hoover-Plow J, Huang M. Lipoprotein(a) metabolism: potential sites for therapeutic targets. Metabolism 2013;62:479–91.PubMedCentralPubMed Hoover-Plow J, Huang M. Lipoprotein(a) metabolism: potential sites for therapeutic targets. Metabolism 2013;62:479–91.PubMedCentralPubMed
121.
Zurück zum Zitat Levy E, Ben Djoudi OA, Spahis S, et al. PCSK9 plays a significant role in cholesterol homeostasis and lipid transport in intestinal epithelial cells. Atherosclerosis 2013;227:297–306.PubMed Levy E, Ben Djoudi OA, Spahis S, et al. PCSK9 plays a significant role in cholesterol homeostasis and lipid transport in intestinal epithelial cells. Atherosclerosis 2013;227:297–306.PubMed
122.
Zurück zum Zitat Sharotri V, Collier DM, Olson DR, et al. Regulation of epithelial sodium channel traficking by proprotein convertase subtilisin/kexin type 9 (PCSK9). J Biol Chem 2012;287:19266–74.PubMedCentralPubMed Sharotri V, Collier DM, Olson DR, et al. Regulation of epithelial sodium channel traficking by proprotein convertase subtilisin/kexin type 9 (PCSK9). J Biol Chem 2012;287:19266–74.PubMedCentralPubMed
123.
Zurück zum Zitat Rashid S, Tavori H, Brown PE, et al. Proprotein convertase subtilisin kexin type 9 promotes intestinal overproduction of triglyceride-rich apolipoprotein B lipoproteins through both low-density lipoprotein receptor- dependent and -independent mechanisms. Circulation 2014;130:431–41.PubMed Rashid S, Tavori H, Brown PE, et al. Proprotein convertase subtilisin kexin type 9 promotes intestinal overproduction of triglyceride-rich apolipoprotein B lipoproteins through both low-density lipoprotein receptor- dependent and -independent mechanisms. Circulation 2014;130:431–41.PubMed
124.
Zurück zum Zitat Le MC, Kourimate S, Langhi C, et al. Proprotein convertase subtilisin kexin type 9 null mice are protected from postprandial triglyceridemia. Arterioscler Thromb Vasc Biol 2009;29:684–90. Le MC, Kourimate S, Langhi C, et al. Proprotein convertase subtilisin kexin type 9 null mice are protected from postprandial triglyceridemia. Arterioscler Thromb Vasc Biol 2009;29:684–90.
125.
Zurück zum Zitat Le MC, Berger JM, Lespine A, et al. Transintestinal cholesterol excretion is an active metabolic process modulated by PCSK9 and statin involving ABCB1. Arterioscler Thromb Vasc Biol 2013;33:1484–93. Le MC, Berger JM, Lespine A, et al. Transintestinal cholesterol excretion is an active metabolic process modulated by PCSK9 and statin involving ABCB1. Arterioscler Thromb Vasc Biol 2013;33:1484–93.
126.
Zurück zum Zitat Abifadel M, Varret M, Rabes JP, et al. Mutations in PCSK9 cause autosomal dominant hypercholesterolemia. Nat Genet 2003;34:154–6.PubMed Abifadel M, Varret M, Rabes JP, et al. Mutations in PCSK9 cause autosomal dominant hypercholesterolemia. Nat Genet 2003;34:154–6.PubMed
127.
Zurück zum Zitat Desai NR, Giugliano RP, Zhou J et al. AMG 145, a monoclonal antibody against PCSK9, facilitates achievement of national cholesterol education program-adult treatment panel III low-density lipoprotein cholesterol goals among high-risk patients: an analysis from the LAPLACE-TIMI 57 trial (LDL-C assessment with PCSK9 monoclonal antibody inhibition combined with statin therapy-thrombolysis in myocardial infarction 57). J Am Coll Cardiol 2014;63:430–3.PubMed Desai NR, Giugliano RP, Zhou J et al. AMG 145, a monoclonal antibody against PCSK9, facilitates achievement of national cholesterol education program-adult treatment panel III low-density lipoprotein cholesterol goals among high-risk patients: an analysis from the LAPLACE-TIMI 57 trial (LDL-C assessment with PCSK9 monoclonal antibody inhibition combined with statin therapy-thrombolysis in myocardial infarction 57). J Am Coll Cardiol 2014;63:430–3.PubMed
128.
Zurück zum Zitat Giuliano RP, Desai NR, Kohli P et al. Efficacy, safety, and tolerability of a monoclonal antibody to proprotein convertase subtilisin/kexin type 9 in combination with a statin in patients with hypercholesterolaemia (LAPLACE-TIMI 57): a randomised, placebo-controlled, dose-ranging, phase 2 study. Lancet 2012;380:2007–17. Giuliano RP, Desai NR, Kohli P et al. Efficacy, safety, and tolerability of a monoclonal antibody to proprotein convertase subtilisin/kexin type 9 in combination with a statin in patients with hypercholesterolaemia (LAPLACE-TIMI 57): a randomised, placebo-controlled, dose-ranging, phase 2 study. Lancet 2012;380:2007–17.
129.
Zurück zum Zitat Desai NR, Kohli P, Giugliano RP et al. AMG145, a monoclonal antibody against proprotein convertase subtilisin kexin type 9, significantly reduces lipoprotein(a) in hypercholesterolemic patients receiving statin therapy: an analysis from the LDL-C Assessment with Proprotein Convertase Subtilisin Kexin Type 9 Monoclonal Antibody Inhibition Combined with Statin Therapy (LAPLACE)-Thrombolysis in Myocardial Infarction (TIMI) 57 trial. Circulation 2013;128:962–9.PubMed Desai NR, Kohli P, Giugliano RP et al. AMG145, a monoclonal antibody against proprotein convertase subtilisin kexin type 9, significantly reduces lipoprotein(a) in hypercholesterolemic patients receiving statin therapy: an analysis from the LDL-C Assessment with Proprotein Convertase Subtilisin Kexin Type 9 Monoclonal Antibody Inhibition Combined with Statin Therapy (LAPLACE)-Thrombolysis in Myocardial Infarction (TIMI) 57 trial. Circulation 2013;128:962–9.PubMed
130.
Zurück zum Zitat Koren MJ, Scott R, Kim JB et al. Efficacy, safety, and tolerability of a monoclonal antibody to proprotein convertase subtilisin/kexin type 9 as monotherapy in patients with hypercholesterolaemia (MENDEL): a randomised, double-blind, placebo-controlled, phase 2 study. Lancet 2012;380:1995–2006.PubMed Koren MJ, Scott R, Kim JB et al. Efficacy, safety, and tolerability of a monoclonal antibody to proprotein convertase subtilisin/kexin type 9 as monotherapy in patients with hypercholesterolaemia (MENDEL): a randomised, double-blind, placebo-controlled, phase 2 study. Lancet 2012;380:1995–2006.PubMed
131.
Zurück zum Zitat Sullivan D, Olsson AG, Scott R et al. Effect of a monoclonal antibody to PCSK9 on low-density lipoprotein cholesterol levels in statin-intolerant patients: the GAUSS randomized trial. JAMA 2012;308:2497–506.PubMed Sullivan D, Olsson AG, Scott R et al. Effect of a monoclonal antibody to PCSK9 on low-density lipoprotein cholesterol levels in statin-intolerant patients: the GAUSS randomized trial. JAMA 2012;308:2497–506.PubMed
132.
Zurück zum Zitat Raal F, Scott R, Somaratne R et al. Low-density lipoprotein cholesterollowering effects of AMG 145, a monoclonal antibody to proprotein convertase subtilisin/kexin type 9 serine protease in patients with heterozygous familial hypercholesterolemia: the Reduction of LDL-C with PCSK9 Inhibition in Heterozygous Familial Hypercholesterolemia Disorder (RUTHERFORD) randomized trial. Circulation 2012;126:2408–17.PubMed Raal F, Scott R, Somaratne R et al. Low-density lipoprotein cholesterollowering effects of AMG 145, a monoclonal antibody to proprotein convertase subtilisin/kexin type 9 serine protease in patients with heterozygous familial hypercholesterolemia: the Reduction of LDL-C with PCSK9 Inhibition in Heterozygous Familial Hypercholesterolemia Disorder (RUTHERFORD) randomized trial. Circulation 2012;126:2408–17.PubMed
133.
Zurück zum Zitat Raal FJ, Stein EA, Dufour R et al. PCSK9 inhibition with evolocumab (AMG 145) in heterozygous familial hypercholesterolaemia (RUTHERFORD- 2): a randomised, double-blind, placebo-controlled trial. Lancet 2014; e-pub ahead of print Raal FJ, Stein EA, Dufour R et al. PCSK9 inhibition with evolocumab (AMG 145) in heterozygous familial hypercholesterolaemia (RUTHERFORD- 2): a randomised, double-blind, placebo-controlled trial. Lancet 2014; e-pub ahead of print
134.
Zurück zum Zitat Koren MJ, Giugliano RP, Raal FJ et al. Efficacy and safety of longer-term administration of evolocumab (AMG 145) in patients with hypercholesterolemia: 52-week results from the Open-Label Study of Long-Term Evaluation Against LDL-C (OSLER) randomized trial. Circulation 2014;129:234–43. Koren MJ, Giugliano RP, Raal FJ et al. Efficacy and safety of longer-term administration of evolocumab (AMG 145) in patients with hypercholesterolemia: 52-week results from the Open-Label Study of Long-Term Evaluation Against LDL-C (OSLER) randomized trial. Circulation 2014;129:234–43.
135.
Zurück zum Zitat Raal FJ, Honarpour N, Blom DJ et al. Inhibition of PCSK9 with evolocumab in homozygous familial hypercholesterolaemia (TESLA Part B): a randomised, double-blind, placebo-controlled trial. Lancet 2014; epub ahead of print. Raal FJ, Honarpour N, Blom DJ et al. Inhibition of PCSK9 with evolocumab in homozygous familial hypercholesterolaemia (TESLA Part B): a randomised, double-blind, placebo-controlled trial. Lancet 2014; epub ahead of print.
136.
Zurück zum Zitat Blom DJ, Hala T, Bolognese M et al. A 52-week placebo-controlled trial of evolocumab in hyperlipidemia. N Engl J Med 2014;370:1809–19.PubMed Blom DJ, Hala T, Bolognese M et al. A 52-week placebo-controlled trial of evolocumab in hyperlipidemia. N Engl J Med 2014;370:1809–19.PubMed
137.
138.
139.
Zurück zum Zitat Robinson J, Farnier M, Krempf M et al. ESC 2014, Barcelona, Spanien, Hot-Line-Session # 707, oral presentation (www.escardio.org/congresses) Robinson J, Farnier M, Krempf M et al. ESC 2014, Barcelona, Spanien, Hot-Line-Session # 707, oral presentation (www.​escardio.​org/congresses)
140.
Zurück zum Zitat Robinson JG, Farnier M, Krempf M. Long-term safety, tolerability and efficacy of alirocumab in high cardiovascular risk patients: ODYSSEY LONG TERM. Efficacy by subgroup, and safety when LDL-C <25 mg/dl. oral presentation AHA 2014 Robinson JG, Farnier M, Krempf M. Long-term safety, tolerability and efficacy of alirocumab in high cardiovascular risk patients: ODYSSEY LONG TERM. Efficacy by subgroup, and safety when LDL-C <25 mg/dl. oral presentation AHA 2014
141.
Zurück zum Zitat Bays H, Gaudet D, Weiss R et al. PCSK9 Inhibitor Alirocumab as Add-on to Atorvastatin versus Other Lipid Treatment Strategies in Patients at High CVD Risk: ODYSSEY OPTIONS I, oral presentation AHA 2014 Bays H, Gaudet D, Weiss R et al. PCSK9 Inhibitor Alirocumab as Add-on to Atorvastatin versus Other Lipid Treatment Strategies in Patients at High CVD Risk: ODYSSEY OPTIONS I, oral presentation AHA 2014
142.
Zurück zum Zitat Bays H, Farnier M, Gaudet D et al. Efficacy And Safety of Combining Alirocumab With Atorvastatin Or Rosuvastatin Versus Statin Intensification Or Adding Ezetimibe In High Cardiovascular Risk Patients: ODYSSEY OPTIONS I and II, oral presentation AHA 2014 Bays H, Farnier M, Gaudet D et al. Efficacy And Safety of Combining Alirocumab With Atorvastatin Or Rosuvastatin Versus Statin Intensification Or Adding Ezetimibe In High Cardiovascular Risk Patients: ODYSSEY OPTIONS I and II, oral presentation AHA 2014
143.
Zurück zum Zitat Moriarty PM, Thompson PD, Cannon P et al. ODYSSEY ALTERNATIVE: Efficacy And Safety Of The Proprotein Convertase Subtilisin/ Kexin Typ 9 Monoclonal Antibody, Alirocumab, Versus Ezetimibe, In Patients With Statin Intolerance As Defined By A Placebo Run-in And Statin Rechallenge Arm, oral presentation AHA 2014. Moriarty PM, Thompson PD, Cannon P et al. ODYSSEY ALTERNATIVE: Efficacy And Safety Of The Proprotein Convertase Subtilisin/ Kexin Typ 9 Monoclonal Antibody, Alirocumab, Versus Ezetimibe, In Patients With Statin Intolerance As Defined By A Placebo Run-in And Statin Rechallenge Arm, oral presentation AHA 2014.
144.
Zurück zum Zitat Ginsberg H, Rader D, Raal FJ et al. ODYSSEY HIGH FH: Efficacy And Safety Of Alirocumab In Patients With Severe Heterozygous Familial Hypercholesterolemia, oral presentation AHA 2014. Ginsberg H, Rader D, Raal FJ et al. ODYSSEY HIGH FH: Efficacy And Safety Of Alirocumab In Patients With Severe Heterozygous Familial Hypercholesterolemia, oral presentation AHA 2014.
145.
Zurück zum Zitat Kereiakes D, Robinson J, Cannon P, et al. Efficacy And Safety Of Alirocumab In High Cardiovascular Risk Patients With Suboptimally Controlled Hypercholesterolemia on Maximally Tolerated Doses Of Statins: The ODYSSEY COMBO I Study, oral presentation AHA 2014 Kereiakes D, Robinson J, Cannon P, et al. Efficacy And Safety Of Alirocumab In High Cardiovascular Risk Patients With Suboptimally Controlled Hypercholesterolemia on Maximally Tolerated Doses Of Statins: The ODYSSEY COMBO I Study, oral presentation AHA 2014
Metadaten
Titel
Neues von ESC und AHA
Perspektiven zu cholesterinwirksamer Behandlung 2014
verfasst von
Prof. Dr. med. Gerald Klose
Rainer Schulz
Wolfgang Koenig
Publikationsdatum
23.12.2014
Verlag
Urban & Vogel
Erschienen in
CardioVasc / Ausgabe 6/2014
Print ISSN: 1617-4933
Elektronische ISSN: 1618-3851
DOI
https://doi.org/10.1007/s15027-014-0521-8

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