nach oben

Erschienen in:

12.12.2017 | Koronare Herzerkrankung | Fortbildung

Glatte Haut, rauhe Gefäße?

Lipidomik identifiziert Ceramide als neue kardiovaskuläre Risikomarker

verfasst von: Prof. Dr. med. Winfried März, Marcus E. Kleber, Hubert Scharnagl, Reijo Laaksonen

Erschienen in: CardioVasc | Ausgabe 6/2017

Einloggen, um Zugang zu erhalten

Zusammenfassung

Ceramide sind komplexe Lipide, die im Organismus vielseitige Aufgaben bei z. B. der Zelldifferenzierung, Signaltransduktion, Apoptose usw. besitzen. Atherosklerotische Plaques sind mit bestimmten Ceramiden stark angereichert. Bei Patienten mit nachgewiesener KHK wurden im Plasma spezifische Cearmide nachgewiesen, die signifikant mit der kardiovaskulären Mortalität korreliert waren.

GBD 2015 Mortality and Causes of Death Collaborators. Global, regional, and national life expectancy, all-cause mortality, and cause-specific mortality for 249 causes of death, 1980-2015: a systematic analysis for the Global Burden of Disease Study 2015. Lancet. 2016;388:1459-544

Stone NJ, Robinson J, 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):S1–45CrossRef

Catapano AL, Graham I, De Backer G et al. 2016 ESC/EAS Guidelines for the Management of Dyslipidaemias: The Task Force for the Management of Dyslipidaemias of the European Society of Cardiology (ESC) and European Atherosclerosis Society (EAS) Developed with the special contribution of the European Assocciation for Cardiovascular Prevention & Rehabilitation (EACPR). Atherosclerosis. 2016;253:281–344CrossRefPubMed

Piepoli MF, Hoes AW, Agewall S et al. 2016 European Guidelines on cardiovascular disease prevention in clinical practice: The Sixth Joint Task Force of the European Society of Cardiology and Other Societies on Cardiovascular Disease Prevention in Clinical Practice (constituted by representatives of 10 societies and by invited experts)Developed with the special contribution of the European Association for Cardiovascular Prevention & Rehabilitation (EACPR). Eur Heart J. 2016;37:2315–81CrossRefPubMedPubMedCentral

Abholz HH, Egidi G, Gries A et al. Nationale Versorgungsleitlinie Therapie des Typ-2-Diabetes. http://wwwleitliniende/mdb/downloads/nvl/diabetes-mellitus/dm-therapie-1aufl-vers4-langpdf 2013 (zuletzt geändert November 2014);Hrsg: Bundesärztekammer, Kassenärztliche Bundesvereinigung, Arbeitsgemeinschaft der Wissenschaftlichen. Medizinischen Fachgesellschaften

Mancia G, Fagard R, Narkiewicz K et al. 2013 ESH/ESC guidelines for the management of arterial hypertension: the Task Force for the Management of Arterial Hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC). Eur Heart J. 2013;34:2159–219CrossRefPubMed

Allan GM, Garrison S, McCormack J. Comparison of cardiovascular disease risk calculators. Curr Opin Lipidol. 2014;25:254–65CrossRefPubMed

Sabatine MS, Giugliano RP, Keech AC et al. Evolocumab and Clinical Outcomes in Patients with Cardiovascular Disease. N Engl J Med. 2017;376:1713–22CrossRefPubMed

Ridker PM, Everett BM, Thuren T et al. Antiinflammatory Therapy with Canakinumab for Atherosclerotic Disease. N Engl J Med. 2017;377:1119–31CrossRefPubMed

10.

Eikelboom JW, Connolly SJ, Bosch J et al. Rivaroxaban with or without Aspirin in Stable Cardiovascular Disease. N Engl J Med. 2017;377:1319–30CrossRefPubMed

11.

Marschner IC, Colquhoun D, Simes RJ et al. Long-term risk stratification for survivors of acute coronary syndromes. Results from the Long-term Intervention with Pravastatin in Ischemic Disease (LIPID) Study. LIPID Study Investigators. J Am Coll Cardiol. 2001;38:56–63CrossRefPubMed

12.

Goliasch G, Kleber ME, Richter B et al. Routinely available biomarkers improve prediction of long-term mortality in stable coronary artery disease: the Vienna and Ludwigshafen Coronary Artery Disease (VILCAD) risk score. Eur Heart J. 2012;33:2282–9CrossRefPubMed

13.

Kleber ME, Goliasch G, Grammer TB et al. Evolving biomarkers improve prediction of long-term mortality in patients with stable coronary artery disease: the BIO-VILCAD score. J Intern Med. 2014;276:184–94CrossRefPubMed

14.

Bohula EA, Morrow DA, Giugliano RP et al. Atherothrombotic Risk Stratification and Ezetimibe for Secondary Prevention. J Am Coll Cardiol. 2017;69:911–21CrossRefPubMed

15.

Lindholm D, Lindback J, Armstrong PW et al. Biomarker-Based Risk Model to Predict Cardiovascular Mortality in Patients With Stable Coronary Disease. J Am Coll Cardiol. 2017;70:813–26CrossRefPubMed

16.

Ravnskov U, Diamond DM, Hama R et al. Lack of an association or an inverse association between low-density-lipoprotein cholesterol and mortality in the elderly: a systematic review. BMJ open. 2016;6:e010401; https://doi.org/10.1136/bmjopen-2015-010401CrossRefPubMedPubMedCentral

17.

Silbernagel G, Schottker B, Appelbaum S et al. High-density lipoprotein cholesterol, coronary artery disease, and cardiovascular mortality. Eur Heart J. 2013;34:3563–71CrossRefPubMed

18.

Sachdeva A, Cannon CP, Deedwania PC et al. Lipid levels in patients hospitalized with coronary artery disease: an analysis of 136,905 hospitalizations in Get With The Guidelines. Am Heart J. 2009;157:111–7.e2CrossRefPubMed

19.

Olsson AG, Schwartz GG, Szarek M et al. High-density lipoprotein, but not low-density lipoprotein cholesterol levels influence short-term prognosis after acute coronary syndrome: results from the MIRACL trial. Eur Heart J. 2005;26:890–6CrossRefPubMed

20.

Puri R, Nissen SE, Libby P et al. C-reactive protein, but not low-density lipoprotein cholesterol levels, associate with coronary atheroma regression and cardiovascular events after maximally intensive statin therapy. Circulation. 2013;128:2395–403CrossRefPubMed

21.

Zewinger S, Kleber ME, Tragante V et al. Relations between lipoprotein(a) concentrations, LPA genetic variants, and the risk of mortality in patients with established coronary heart disease: a molecular and genetic association study. Lancet Diabetes Endocrinol. 2017;5:534–43CrossRefPubMed

22.

Triebl A, Hartler J, Trotzmüller M, Köfeler HC. Lipidomics: Prospects from a technological perspective. Biochim Biophys Acta. 2017;1862:740–6CrossRefPubMed

23.

Gross RW. The evolution of lipidomics through space and time. Biochim Biophys Acta. 2017;1862:731–9CrossRefPubMed

24.

Laaksonen R. Identifying new Risk Markers and Potential Targets for Coronary Artery Disease: The Value of the Lipidome and Metabolome. Cardiovasc Drugs Ther. 2016;30:19–32CrossRefPubMed

25.

Tarasov K, Ekroos K, Suoniemi M et al. Molecular lipids identify cardiovascular risk and are efficiently lowered by simvastatin and PCSK9 deficiency. J Clin Endocrinol Metab. 2014;99:E45–52CrossRefPubMed

26.

Borodzicz S, Czarzasta K, Kuch M, Cudnoch-Jedrzejewska A. Sphingolipids in cardiovascular diseases and metabolic disorders. Lipids Health Dis. 2015;14:55CrossRefPubMedPubMedCentral

27.

Chaurasia B, Summers SA. Ceramides - Lipotoxic Inducers of Metabolic Disorders. Trends Endocrinol Metab. 2015;26:538–50CrossRefPubMed

28.

Schissel SL, Tweedie-Hardman J, Rapp JH et al. Rabbit aorta and human atherosclerotic lesions hydrolyze the sphingomyelin of retained low-density lipoprotein. Proposed role for arterial-wall sphingomyelinase in subendothelial retention and aggregation of atherogenic lipoproteins. J Clin Invest. 1996;98:1455–64CrossRefPubMedPubMedCentral

29.

Marathe S, Schissel SL, Yellin MJ et al. Human vascular endothelial cells are a rich and regulatable source of secretory sphingomyelinase. Implications for early atherogenesis and ceramide-mediated cell signaling. J Biol Chem. 1998;273:4081–8CrossRefPubMed

30.

Fekry B, Esmaeilniakooshkghazi A, Krupenko SA, Krupenko NI. Ceramide Synthase 6 Is a Novel Target of Methotrexate Mediating Its Antiproliferative Effect in a p53-Dependent Manner. PLoS One 2016;11:e0146618, https://doi.org/10.1371/journal.pone.0146618CrossRefPubMedPubMedCentral

31.

Spijkers LJ, van den Akker RF, Janssen BJ et al. Hypertension is associated with marked alterations in sphingolipid biology: a potential role for ceramide. PLoS One 2011;6:e21817; https://doi.org/10.1371/journal.pone.0021817CrossRefPubMedPubMedCentral

32.

Bergman BC, Brozinick JT, Strauss A et al. Serum sphingolipids: relationships to insulin sensitivity and changes with exercise in humans. Am J Physiol Endocrinol Metab. 2015;309:E398–408CrossRefPubMedPubMedCentral

33.

Huang H, Kasumov T, Gatmaitan P et al. Gastric bypass surgery reduces plasma ceramide subspecies and improves insulin sensitivity in severely obese patients. Obesity (Silver Spring). 2011;19:2235–40CrossRefPubMed

34.

Haus JM, Kashyap SR, Kasumov T et al. Plasma ceramides are elevated in obese subjects with type 2 diabetes and correlate with the severity of insulin resistance. Diabetes. 2009;58:337–43CrossRefPubMedPubMedCentral

35.

Predescu S, Knezevic I, Bardita C et al. Platelet activating factor-induced ceramide micro-domains drive endothelial NOS activation and contribute to barrier dysfunction. PLoS One 2013;8:e75846, https://doi.org/10.1371/journal.pone.0075846CrossRefPubMedPubMedCentral

36.

Li W, Yang X, Xing S et al. Endogenous ceramide contributes to the transcytosis of oxLDL across endothelial cells and promotes its subendothelial retention in vascular wall. Oxid Med Cell Longev. 2014;2014:1–11

37.

Cheng JM, Suoniemi M, Kardys I et al. Plasma concentrations of molecular lipid species in relation to coronary plaque characteristics and cardiovascular outcome: Results of the ATHEROREMO-IVUS study. Atherosclerosis. 2015;243:560–6CrossRefPubMed

38.

Havulinna AS, Sysi-Aho M, Hilvo M et al. Circulating Ceramides Predict Cardiovascular Outcomes in the Population-Based FINRISK 2002 Cohort. Arterioscler Thromb Vasc Biol. 2016;36:2424–30CrossRefPubMed

39.

Laaksonen R, Ekroos K, Sysi-Aho M et al. Plasma ceramides predict cardiovascular death in patients with stable coronary artery disease and acute coronary syndromes beyond LDL-cholesterol. Eur Heart J. 2016;37:1967–76CrossRefPubMedPubMedCentral

40.

Menuz V, Howell KS, Gentina S et al. Protection of C. elegans from anoxia by HYL-2 ceramide synthase. Science. 2009;324:381–4CrossRefPubMed

41.

Park JW, Park WJ, Futerman AH. Ceramide synthases as potential targets for therapeutic intervention in human diseases. Biochim Biophys Acta. 2014;1841:671–81CrossRefPubMed

42.

Turpin SM, Nicholls HT, Willmes DM et al. Obesity-induced CerS6-dependent C16:0 ceramide production promotes weight gain and glucose intolerance. Cell Metab. 2014;20:678–86CrossRefPubMed

43.

Raichur S, Wang ST, Chan PW et al. CerS2 haploinsufficiency inhibits beta-oxidation and confers susceptibility to diet-induced steatohepatitis and insulin resistance. Cell Metab. 2014;20:687–95CrossRefPubMed

44.

Hlatky MA, Greenland P, Arnett DK et al. Criteria for evaluation of novel markers of cardiovascular risk: a scientific statement from the American Heart Association. Circulation. 2009;119:2408–16CrossRefPubMedPubMedCentral

45.

Ng TW, Ooi EM, Watts GF et al. Dose-dependent effects of rosuvastatin on the plasma sphingolipidome and phospholipidome in the metabolic syndrome. J Clin Endocrinol Metab. 2014;99:E2335–40CrossRefPubMed

46.

Saied EM, Arenz C. Small molecule inhibitors of ceramidases. Cell Physiol Biochem. 2014;34:197–212CrossRefPubMed

47.

Laufs U, Scharnagl H, Marz W. Statin intolerance. Curr Opin Lipidol. 2015;26:492–501CrossRefPubMed

48.

Walters MJ, Wrenn SP. Effect of sphingomyelinase-mediated generation of ceramide on aggregation of low-density lipoprotein. Langmuir. 2008;24:9642–7CrossRefPubMed

49.

Nixon GF. Sphingolipids in inflammation: pathological implications and potential therapeutic targets. Br J Pharmacol. 2009;158:982–93CrossRefPubMedPubMedCentral

50.

Xu J, Yeh CH, Chen S et al. Involvement of de novo ceramide biosynthesis in tumor necrosis factor-alpha/cycloheximide-induced cerebral endothelial cell death. J Biol Chem. 1998;273:16521–6CrossRefPubMed

51.

Modur V, Zimmerman GA, Prescott SM, McIntyre TM. Endothelial cell inflammatory responses to tumor necrosis factor alpha. Ceramide-dependent and -independent mitogen-activated protein kinase cascades. J Biol Chem. 1996;271:13094–102CrossRefPubMed

52.

Zhang DX, Zou AP, Li PL. Ceramide reduces endothelium-dependent vasodilation by increasing superoxide production in small bovine coronary arteries. Cir Res. 2001;88:824–31CrossRef

53.

Gomez-Munoz A, Presa N, Gomez-Larrauri A et al. Control of inflammatory responses by ceramide, sphingosine 1-phosphate and ceramide 1-phosphate. Prog Lipid Res. 2016;61:51–62CrossRefPubMed

Titel: Glatte Haut, rauhe Gefäße?
Lipidomik identifiziert Ceramide als neue kardiovaskuläre Risikomarker
verfasst von: Prof. Dr. med. Winfried März
Marcus E. Kleber
Hubert Scharnagl
Reijo Laaksonen
Publikationsdatum: 12.12.2017
Verlag: Springer Medizin
Schlagwort: Koronare Herzerkrankung
Erschienen in: CardioVasc / Ausgabe 6/2017
Print ISSN: 1617-4933
Elektronische ISSN: 1618-3851
DOI: https://doi.org/10.1007/s15027-017-1276-9

Neu im Fachgebiet Kardiologie

Screening-Mammografie offenbart erhöhtes Herz-Kreislauf-Risiko

26.04.2024 Mammografie Nachrichten

Routinemäßige Mammografien helfen, Brustkrebs frühzeitig zu erkennen. Anhand der Röntgenuntersuchung lassen sich aber auch kardiovaskuläre Risikopatientinnen identifizieren. Als zuverlässiger Anhaltspunkt gilt die Verkalkung der Brustarterien.

Niedriger diastolischer Blutdruck erhöht Risiko für schwere kardiovaskuläre Komplikationen

25.04.2024 Hypotonie Nachrichten

Wenn unter einer medikamentösen Hochdrucktherapie der diastolische Blutdruck in den Keller geht, steigt das Risiko für schwere kardiovaskuläre Ereignisse: Darauf deutet eine Sekundäranalyse der SPRINT-Studie hin.

Therapiestart mit Blutdrucksenkern erhöht Frakturrisiko

25.04.2024 Hypertonie Nachrichten

Beginnen ältere Männer im Pflegeheim eine Antihypertensiva-Therapie, dann ist die Frakturrate in den folgenden 30 Tagen mehr als verdoppelt. Besonders häufig stürzen Demenzkranke und Männer, die erstmals Blutdrucksenker nehmen. Dafür spricht eine Analyse unter US-Veteranen.

Adipositas-Medikament auch gegen Schlafapnoe wirksam

24.04.2024 Adipositas Nachrichten

Der als Antidiabetikum sowie zum Gewichtsmanagement zugelassene Wirkstoff Tirzepatid hat in Studien bei adipösen Patienten auch schlafbezogene Atmungsstörungen deutlich reduziert, informiert der Hersteller in einer Vorab-Meldung zum Studienausgang.

Update Kardiologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.

Newsletter bestellen

Springer Medizin

Zusammenfassung

Bitte loggen Sie sich ein, um Zugang zu diesem Inhalt zu erhalten

Weitere Artikel der Ausgabe 6/2017

Kontroverse über die Qualitätssicherung in der Kardiologie

Ist der Herzkatheter ein Placebo?

Brisante Studie bringt Kardiologie-Welt durcheinander

CASTLE-AF — ein Meilenstein für die Rhythmologie