Skip to main content
Top
Published in: Current Atherosclerosis Reports 3/2012

01-06-2012 | Genetics (AJ Marian, Section Editor)

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

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

Published in: Current Atherosclerosis Reports | Issue 3/2012

Login to get access

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.
Literature
2.
go back to reference • 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.
go back to reference 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.
go back to reference 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.•
go back to reference 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.
go back to reference 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.
go back to reference 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.
go back to reference 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.
go back to reference 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.
go back to reference 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.
go back to reference 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.
go back to reference 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.
go back to reference • 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.
go back to reference 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.
go back to reference 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.
go back to reference 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.
go back to reference 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.
go back to reference 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.
go back to reference 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.
go back to reference 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.
go back to reference 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.
go back to reference • 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.
go back to reference 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.
go back to reference • 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.
go back to reference 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.
go back to reference 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.
go back to reference 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.
go back to reference 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.
go back to reference 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.
go back to reference 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.
go back to reference 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.
go back to reference • 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.
go back to reference 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.
go back to reference 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.
go back to reference 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.
go back to reference 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.
go back to reference 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.
go back to reference 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.
go back to reference 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.
go back to reference 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.
go back to reference 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
Metadata
Title
Atherosclerosis, Inflammation, Genetics, and Stem Cells: 2012 Update
Authors
Pascal J. Goldschmidt-Clermont
Chunming Dong
David M. Seo
Omaida C. Velazquez
Publication date
01-06-2012
Publisher
Current Science Inc.
Published in
Current Atherosclerosis Reports / Issue 3/2012
Print ISSN: 1523-3804
Electronic ISSN: 1534-6242
DOI
https://doi.org/10.1007/s11883-012-0244-1

Other articles of this Issue 3/2012

Current Atherosclerosis Reports 3/2012 Go to the issue

Vascular Biology (RS Rosenson, Section Editor)

Myeloperoxidase Production by Macrophage and Risk of Atherosclerosis

Genetics (AJ Marian, Section Editor)

Sortilin as a Regulator of Lipoprotein Metabolism

Genetics (AJ Marian, Section Editor)

Genetics of Thoracic Aortic Aneurysms

Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Watch this official video from ACC.24. Dr. Biykem Bozkurt discuss last year's major advances in heart failure and cardiomyopathies.