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Erschienen in: Current Atherosclerosis Reports 3/2012

01.06.2012 | Genetics (AJ Marian, Section Editor)

Atherosclerosis, Inflammation, Genetics, and Stem Cells: 2012 Update

verfasst von: Pascal J. Goldschmidt-Clermont, Chunming Dong, David M. Seo, Omaida C. Velazquez

Erschienen in: Current Atherosclerosis Reports | Ausgabe 3/2012

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Abstract

Atherosclerosis is a peculiar form of inflammation triggered by cholesterol-rich lipoproteins and other noxious factors such as cigarette smoke, diabetes mellitus, and hypertension. Genetics also play an important role in the disease, accounting for about 40% of the risk. Of surprise in recent years of post-human genome sequencing, atherosclerosis-relevant genes discovered by non-biased techniques (ie, genome-wide association studies), did not rehash previously suspected pathways of lipid metabolism, diabetes, or hypertension. Instead these studies highlighted genes relevant to mechanisms of inflammation and stem cell biology. Only a minority of implicated genes were linked to lipid and other cardiac risk factor genes. Although such findings do not contradict the fact that atherosclerosis is triggered and exacerbated by elevated lipids, atherosclerosis “new genes” suggest that the mechanism responsible for the development of arterial lesions is more complex than a simple response to injury, where injury is necessary, but perhaps not sufficient, for disease progression.
Literatur
1.
2.
Zurück zum Zitat • Libby P, Ridker PM, Hansson GK. Progress and challenges in translating the biology of atherosclerosis. Nature. 2011;473(7347):317–25. Review. This is a thorough review of the most recent information on atherosclerosis inflammation and its cellular and molecular agents. Novel clinical trials with anti-inflammatory drugs are also surveyed.PubMedCrossRef • Libby P, Ridker PM, Hansson GK. Progress and challenges in translating the biology of atherosclerosis. Nature. 2011;473(7347):317–25. Review. This is a thorough review of the most recent information on atherosclerosis inflammation and its cellular and molecular agents. Novel clinical trials with anti-inflammatory drugs are also surveyed.PubMedCrossRef
3.
Zurück zum Zitat Karra R, Vemullapalli S, Dong C, et al. Molecular evidence for arterial repair in atherosclerosis. Proc Natl Acad Sci USA. 2005;102(46):16789–94.PubMedCrossRef Karra R, Vemullapalli S, Dong C, et al. Molecular evidence for arterial repair in atherosclerosis. Proc Natl Acad Sci USA. 2005;102(46):16789–94.PubMedCrossRef
4.
Zurück zum Zitat Ridker PM, Rifai N, Rose L, Buring JE, Cook NR. Comparison of C-reactive protein and low-density lipoprotein cholesterol levels in the prediction of first cardiovascular events. N Engl J Med. 2002;347(20):1557–65.PubMedCrossRef Ridker PM, Rifai N, Rose L, Buring JE, Cook NR. Comparison of C-reactive protein and low-density lipoprotein cholesterol levels in the prediction of first cardiovascular events. N Engl J Med. 2002;347(20):1557–65.PubMedCrossRef
6.•
Zurück zum Zitat Stylianou IM, Bauer RC, Reilly MP, Rader DJ. Genetic basis of atherosclerosis: insights from mice and humans. Circ Res. 2012. In press. This is a well-written review of the genetic (epigenetic) discoveries relative to atherosclerosis in mice and humans. It is probably the most complete review to date on the topic. Stylianou IM, Bauer RC, Reilly MP, Rader DJ. Genetic basis of atherosclerosis: insights from mice and humans. Circ Res. 2012. In press. This is a well-written review of the genetic (epigenetic) discoveries relative to atherosclerosis in mice and humans. It is probably the most complete review to date on the topic.
7.
Zurück zum Zitat Galbut DL, Traad EA, Dorman MJ, et al. Twelve-year experience with bilateral internal mammary artery grafts. Ann Thorac Surg. 1985;40(3):264–70.PubMedCrossRef Galbut DL, Traad EA, Dorman MJ, et al. Twelve-year experience with bilateral internal mammary artery grafts. Ann Thorac Surg. 1985;40(3):264–70.PubMedCrossRef
8.
Zurück zum Zitat Loop FD, Lytle BW, Cosgrove DM, et al. Influence of the internal-mammary-artery graft on 10-year survival and other cardiac events. N Engl J Med. 1986;314(1):1–6.PubMedCrossRef Loop FD, Lytle BW, Cosgrove DM, et al. Influence of the internal-mammary-artery graft on 10-year survival and other cardiac events. N Engl J Med. 1986;314(1):1–6.PubMedCrossRef
9.
Zurück zum Zitat Kurlansky PA, Traad EA, Dorman MJ, et al. Thirty-year follow-up defines survival benefit for second internal mammary artery in propensity-matched groups. Ann Thorac Surg. 2010;90:101–8.PubMedCrossRef Kurlansky PA, Traad EA, Dorman MJ, et al. Thirty-year follow-up defines survival benefit for second internal mammary artery in propensity-matched groups. Ann Thorac Surg. 2010;90:101–8.PubMedCrossRef
10.
Zurück zum Zitat Kurlansky PA, Traad EA, Dorman MJ, et al. Location of the second internal mammary artery graft does not influence outcome of coronary artery bypass grafting. Ann Thorac Surg. 2011;91(5):1378–83.PubMedCrossRef Kurlansky PA, Traad EA, Dorman MJ, et al. Location of the second internal mammary artery graft does not influence outcome of coronary artery bypass grafting. Ann Thorac Surg. 2011;91(5):1378–83.PubMedCrossRef
11.
Zurück zum Zitat Goldschmidt-Clermont PJ. Loss of bone marrow-derived vascular progenitor cells leads to inflammation and atherosclerosis. Am Heart J. 2003;146 Suppl 4:S5–S12.PubMedCrossRef Goldschmidt-Clermont PJ. Loss of bone marrow-derived vascular progenitor cells leads to inflammation and atherosclerosis. Am Heart J. 2003;146 Suppl 4:S5–S12.PubMedCrossRef
12.
Zurück zum Zitat Xiao Q, Kiechl S, Patel S, et al. Endothelial progenitor cells, cardiovascular risk factors, cytokine levels and atherosclerosis – Results from a large population-based study. PLoS One. 2007;2(10):e975.PubMedCrossRef Xiao Q, Kiechl S, Patel S, et al. Endothelial progenitor cells, cardiovascular risk factors, cytokine levels and atherosclerosis – Results from a large population-based study. PLoS One. 2007;2(10):e975.PubMedCrossRef
13.
Zurück zum Zitat Rauscher FM, Goldschmidt-Clermont PJ, Davis BH, et al. Aging, progenitor cell exhaustion, and atherosclerosis. Circulation. 2003;108(4):457–63.PubMedCrossRef Rauscher FM, Goldschmidt-Clermont PJ, Davis BH, et al. Aging, progenitor cell exhaustion, and atherosclerosis. Circulation. 2003;108(4):457–63.PubMedCrossRef
14.
Zurück zum Zitat • Song X, Ma Q, Liu X, et al. Will periodic intravenous injections of conditioned bone marrow cells effectively reduce atherosclerosis? Antioxid Redox Signal. 2012;16(1):85–91. This is the first report on reduction of atherosclerosis by some 80% in ApoE−/− mice without altering the lipidic injury (6 g/L) and without additional genetic intervention, using repeated infusions of cultured lineage-negative bone marrow cells in enhanced conditions.PubMedCrossRef • Song X, Ma Q, Liu X, et al. Will periodic intravenous injections of conditioned bone marrow cells effectively reduce atherosclerosis? Antioxid Redox Signal. 2012;16(1):85–91. This is the first report on reduction of atherosclerosis by some 80% in ApoE−/− mice without altering the lipidic injury (6 g/L) and without additional genetic intervention, using repeated infusions of cultured lineage-negative bone marrow cells in enhanced conditions.PubMedCrossRef
15.
Zurück zum Zitat Harris TB, Ferrucci L, Tracy RP, et al. Associations of elevated interleukin-6 and C-reactive protein levels with mortality in the elderly. Am J Med. 1999;106(5):506–12.PubMedCrossRef Harris TB, Ferrucci L, Tracy RP, et al. Associations of elevated interleukin-6 and C-reactive protein levels with mortality in the elderly. Am J Med. 1999;106(5):506–12.PubMedCrossRef
16.
Zurück zum Zitat Goldschmidt-Clermont PJ, Creager MA, Losordo DW, et al. Atherosclerosis 2005: recent discoveries and novel hypotheses. Circulation. 2005;112(21):3348–53.PubMedCrossRef Goldschmidt-Clermont PJ, Creager MA, Losordo DW, et al. Atherosclerosis 2005: recent discoveries and novel hypotheses. Circulation. 2005;112(21):3348–53.PubMedCrossRef
18.
Zurück zum Zitat Gutstein DE, Fuster V. Pathophysiology and clinical significance of atherosclerotic plaque rupture. Cardiovasc Res. 1999;41(2):323–33.PubMedCrossRef Gutstein DE, Fuster V. Pathophysiology and clinical significance of atherosclerotic plaque rupture. Cardiovasc Res. 1999;41(2):323–33.PubMedCrossRef
19.
Zurück zum Zitat Khurana R, Simons M, Martin JF, Zachary IC. Role of angiogenesis in cardiovascular disease: a critical appraisal. Circulation. 2005;112(12):1813–24. Review.PubMedCrossRef Khurana R, Simons M, Martin JF, Zachary IC. Role of angiogenesis in cardiovascular disease: a critical appraisal. Circulation. 2005;112(12):1813–24. Review.PubMedCrossRef
20.
Zurück zum Zitat Majesky MW, Dong XR, Hoglund V, Daum G, Mahoney Jr WM. The adventitia: a progenitor cell niche for the vessel wall. Cells Tissues Organs. 2012;195(1–2):73–81.PubMedCrossRef Majesky MW, Dong XR, Hoglund V, Daum G, Mahoney Jr WM. The adventitia: a progenitor cell niche for the vessel wall. Cells Tissues Organs. 2012;195(1–2):73–81.PubMedCrossRef
21.
Zurück zum Zitat Asahara T, Murohara T, Sullivan A, et al. Isolation of putative progenitor endothelial cells for angiogenesis. Science. 1997;275(5302):964–7.PubMedCrossRef Asahara T, Murohara T, Sullivan A, et al. Isolation of putative progenitor endothelial cells for angiogenesis. Science. 1997;275(5302):964–7.PubMedCrossRef
22.
Zurück zum Zitat Hill JM, Zalos G, Halcox JP, et al. Circulating endothelial progenitor cells, vascular function, and cardiovascular risk. N Engl J Med. 2003;348(7):593–600.PubMedCrossRef Hill JM, Zalos G, Halcox JP, et al. Circulating endothelial progenitor cells, vascular function, and cardiovascular risk. N Engl J Med. 2003;348(7):593–600.PubMedCrossRef
23.
Zurück zum Zitat Zhu S, Evans S, Yan B, et al. Transcriptional regulation of Bim by FOXO3a and Akt mediates scleroderma serum-induced apoptosis in endothelial progenitor cells. Circulation. 2008;118(21):2156–65.PubMedCrossRef Zhu S, Evans S, Yan B, et al. Transcriptional regulation of Bim by FOXO3a and Akt mediates scleroderma serum-induced apoptosis in endothelial progenitor cells. Circulation. 2008;118(21):2156–65.PubMedCrossRef
24.
Zurück zum Zitat • Goldschmidt-Clermont PJ, Seo DM, Wang L, et al. Inflammation, stem cells and atherosclerosis genetics. Curr Opin Mol Ther. 2010;12(6):712–23. Review. This is a prior review by our group addressing the genetic revolution triggered by serial GWAS that unveiled an unanticipated series of genomic loci relative to our understanding of atherosclerosis.PubMed • Goldschmidt-Clermont PJ, Seo DM, Wang L, et al. Inflammation, stem cells and atherosclerosis genetics. Curr Opin Mol Ther. 2010;12(6):712–23. Review. This is a prior review by our group addressing the genetic revolution triggered by serial GWAS that unveiled an unanticipated series of genomic loci relative to our understanding of atherosclerosis.PubMed
25.
Zurück zum Zitat Sivapalaratnam S, Motazacker MM, Maiwald S, et al. Genome-wide association studies in atherosclerosis. Curr Atheroscler Rep. 2011;13(3):225–32. Review.PubMedCrossRef Sivapalaratnam S, Motazacker MM, Maiwald S, et al. Genome-wide association studies in atherosclerosis. Curr Atheroscler Rep. 2011;13(3):225–32. Review.PubMedCrossRef
26.
Zurück zum Zitat • Lund G, Zaina S. Atherosclerosis: an epigenetic balancing act that goes wrong. Curr Atheroscler Rep. 2011;13(3):208–14. Review. This is a review how dietary components could induce atherosclerotic atherosclerosis through epigenetic changes that shift the physiologic program of differential gene activation and repression.PubMedCrossRef • Lund G, Zaina S. Atherosclerosis: an epigenetic balancing act that goes wrong. Curr Atheroscler Rep. 2011;13(3):208–14. Review. This is a review how dietary components could induce atherosclerotic atherosclerosis through epigenetic changes that shift the physiologic program of differential gene activation and repression.PubMedCrossRef
27.
Zurück zum Zitat Manolio TA, Green ED. Genomics reaches the clinic: from basic discoveries to clinical impact. Cell. 2011;147:14–6.PubMedCrossRef Manolio TA, Green ED. Genomics reaches the clinic: from basic discoveries to clinical impact. Cell. 2011;147:14–6.PubMedCrossRef
28.
29.
Zurück zum Zitat Barbalic M, Reiner AP, Wu C, et al. Genome-wide association analysis of incident coronary heart disease (CHD) in African Americans: a short report. PLoS Genet. 2011;7(8):e1002199. Epub 2011 Aug 4.PubMedCrossRef Barbalic M, Reiner AP, Wu C, et al. Genome-wide association analysis of incident coronary heart disease (CHD) in African Americans: a short report. PLoS Genet. 2011;7(8):e1002199. Epub 2011 Aug 4.PubMedCrossRef
30.
Zurück zum Zitat Wang F, Xu CQ, He Q, et al. Genome-wide association identifies a susceptibility locus for coronary artery disease in the Chinese Han population. Nat Genet. 2011;43(4):345–9.PubMedCrossRef Wang F, Xu CQ, He Q, et al. Genome-wide association identifies a susceptibility locus for coronary artery disease in the Chinese Han population. Nat Genet. 2011;43(4):345–9.PubMedCrossRef
31.
Zurück zum Zitat Roger VL, Go AS, Lloyd-Jones DM, et al. on behalf of the American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Heart disease and stroke statistics--2012 update: a report from the American Heart Association. Circulation. 2011;123(4):e18–e209. Roger VL, Go AS, Lloyd-Jones DM, et al. on behalf of the American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Heart disease and stroke statistics--2012 update: a report from the American Heart Association. Circulation. 2011;123(4):e18–e209.
32.
Zurück zum Zitat Kim HO, Jin Y, Kickler TS, et al. Gene frequencies of the five major human platelet antigens in African American, white, and Korean populations. Transfusion. 1995;35(10):863–7.PubMedCrossRef Kim HO, Jin Y, Kickler TS, et al. Gene frequencies of the five major human platelet antigens in African American, white, and Korean populations. Transfusion. 1995;35(10):863–7.PubMedCrossRef
33.
Zurück zum Zitat Weiss EJ, Bray PF, Tayback M, et al. A polymorphism of a platelet glycoprotein receptor as an inherited risk factor for coronary thrombosis. N Engl J Med. 1996;334(17):1090–4.PubMedCrossRef Weiss EJ, Bray PF, Tayback M, et al. A polymorphism of a platelet glycoprotein receptor as an inherited risk factor for coronary thrombosis. N Engl J Med. 1996;334(17):1090–4.PubMedCrossRef
34.
Zurück zum Zitat Kucharska-Newton AM, Monda KL, Campbell S, et al. Association of the platelet GPIIb/IIIa polymorphism with atherosclerotic plaque morphology: the Atherosclerosis Risk in Communities (ARIC) Study. Atherosclerosis. 2011;216(1):151–6.PubMedCrossRef Kucharska-Newton AM, Monda KL, Campbell S, et al. Association of the platelet GPIIb/IIIa polymorphism with atherosclerotic plaque morphology: the Atherosclerosis Risk in Communities (ARIC) Study. Atherosclerosis. 2011;216(1):151–6.PubMedCrossRef
35.
Zurück zum Zitat • Schunkert H, König IR, Kathiresan S, et al. CARDIoGRAM Consortium, Samani NJ: large-scale association analysis identifies 13 new susceptibility loci for coronary artery disease. Nat Genet. 2011;43(4):333–8. The CARDIoGram Consortium is a comprehensive analysis (GWAS) of very large cohorts to identify SNPs that significantly associate with CHD. The study not only confirmed previously identified SNPs, but also pointed to 13 new, not previously recognized SNPs.PubMedCrossRef • Schunkert H, König IR, Kathiresan S, et al. CARDIoGRAM Consortium, Samani NJ: large-scale association analysis identifies 13 new susceptibility loci for coronary artery disease. Nat Genet. 2011;43(4):333–8. The CARDIoGram Consortium is a comprehensive analysis (GWAS) of very large cohorts to identify SNPs that significantly associate with CHD. The study not only confirmed previously identified SNPs, but also pointed to 13 new, not previously recognized SNPs.PubMedCrossRef
36.
Zurück zum Zitat Coronary Artery Disease (C4D) Genetics Consortium. A genome-wide association study in Europeans and South Asians identifies five new loci for coronary artery disease. Nat Genet. 2011;43(4):339–44.CrossRef Coronary Artery Disease (C4D) Genetics Consortium. A genome-wide association study in Europeans and South Asians identifies five new loci for coronary artery disease. Nat Genet. 2011;43(4):339–44.CrossRef
37.
Zurück zum Zitat Iannitti T, Palmieri B. Inflammation and genetics: an insight in the centenarian model. Hum Biol. 2011;83(4):531–59.PubMedCrossRef Iannitti T, Palmieri B. Inflammation and genetics: an insight in the centenarian model. Hum Biol. 2011;83(4):531–59.PubMedCrossRef
38.
Zurück zum Zitat Samani NJ, Erdmann J, Hall AS, et al. WTCCC and the Cardiogenics Consortium: genomewide association analysis of coronary artery disease. N Engl J Med. 2007;357(5):443–53.PubMedCrossRef Samani NJ, Erdmann J, Hall AS, et al. WTCCC and the Cardiogenics Consortium: genomewide association analysis of coronary artery disease. N Engl J Med. 2007;357(5):443–53.PubMedCrossRef
39.
Zurück zum Zitat Zernecke A, Bidzhekov K, Noels H, et al. Delivery of microRNA-126 by apoptotic bodies induces CXCL12-dependent vascular protection. Sci Signal. 2009;2(100):ra81.PubMedCrossRef Zernecke A, Bidzhekov K, Noels H, et al. Delivery of microRNA-126 by apoptotic bodies induces CXCL12-dependent vascular protection. Sci Signal. 2009;2(100):ra81.PubMedCrossRef
40.
Zurück zum Zitat Mause SF, Ritzel E, Liehn EA, et al. Platelet microparticles enhance the vasoregenerative potential of angiogenic early outgrowth cells after vascular injury. Circulation. 2010;122(5):495–506.PubMedCrossRef Mause SF, Ritzel E, Liehn EA, et al. Platelet microparticles enhance the vasoregenerative potential of angiogenic early outgrowth cells after vascular injury. Circulation. 2010;122(5):495–506.PubMedCrossRef
41.
Zurück zum Zitat Hristov M, Zernecke A, Weber C. Regulation of endothelial progenitor cell homing after arterial injury. Thromb Haemost. 2007;98(2):274–7.PubMed Hristov M, Zernecke A, Weber C. Regulation of endothelial progenitor cell homing after arterial injury. Thromb Haemost. 2007;98(2):274–7.PubMed
42.
Zurück zum Zitat Hristov M, Zernecke A, Bidzhekov K, et al. Importance of CXC chemokine receptor 2 in the homing of human peripheral blood endothelial progenitor cells to sites of arterial injury. Circ Res. 2007;100(4):590–7.PubMedCrossRef Hristov M, Zernecke A, Bidzhekov K, et al. Importance of CXC chemokine receptor 2 in the homing of human peripheral blood endothelial progenitor cells to sites of arterial injury. Circ Res. 2007;100(4):590–7.PubMedCrossRef
43.
Zurück zum Zitat Liehn EA, Tuchscheerer N, Kanzler I, et al. Double-edged role of the CXCL12/CXCR4 axis in experimental myocardial infarction. J Am Coll Cardiol. 2011;58(23):2415–23.PubMedCrossRef Liehn EA, Tuchscheerer N, Kanzler I, et al. Double-edged role of the CXCL12/CXCR4 axis in experimental myocardial infarction. J Am Coll Cardiol. 2011;58(23):2415–23.PubMedCrossRef
44.
Zurück zum Zitat Archacki SR, Angheloiu G, Moravec CS, et al. Comparative gene expression analysis between coronary arteries and internal mammary arteries identifies a role for the TES gene in endothelial cell functions relevant to coronary artery disease. Hum Mol Genet. 2011. doi:10.1093hmg/ddr574 Archacki SR, Angheloiu G, Moravec CS, et al. Comparative gene expression analysis between coronary arteries and internal mammary arteries identifies a role for the TES gene in endothelial cell functions relevant to coronary artery disease. Hum Mol Genet. 2011. doi:10.​1093hmg/​ddr574
Metadaten
Titel
Atherosclerosis, Inflammation, Genetics, and Stem Cells: 2012 Update
verfasst von
Pascal J. Goldschmidt-Clermont
Chunming Dong
David M. Seo
Omaida C. Velazquez
Publikationsdatum
01.06.2012
Verlag
Current Science Inc.
Erschienen in
Current Atherosclerosis Reports / Ausgabe 3/2012
Print ISSN: 1523-3804
Elektronische ISSN: 1534-6242
DOI
https://doi.org/10.1007/s11883-012-0244-1

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