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01-10-2013 | Clinical Trials and Their Interpretations (J Plutzky, Section Editor)

Update on Lipoprotein(a) as a Cardiovascular Risk Factor and Mediator

Authors: Michael B. Boffa, Marlys L. Koschinsky

Published in: Current Atherosclerosis Reports | Issue 10/2013

Abstract

Recent genetic studies have put the spotlight back onto lipoprotein(a) [Lp(a)] as a causal risk factor for coronary heart disease. However, there remain significant gaps in our knowledge with respect to how the Lp(a) particle is assembled, the route of its catabolism, and the mechanism(s) of Lp(a) pathogenicity. It has long been speculated that the effects of Lp(a) in the vasculature can be attributed to both its low-density lipoprotein moiety and the unique apolipoprotein(a) component, which is strikingly similar to the kringle-containing fibrinolytic zymogen plasminogen. However, the ability of Lp(a) to modulate either purely thrombotic or purely atherothrombotic processes in vivo remains unclear. The presence of oxidized phospholipid on Lp(a) may underlie many of the proatherosclerotic effects of Lp(a) that have been identified both in cell models and in animal models, and provides a possible avenue for identifying therapeutics aimed at mitigating the effects of Lp(a) in the vasculature. However, the beneficial effects of targeted Lp(a) therapeutics, designed to either lower Lp(a) concentrations or interfere with its effects, on cardiovascular outcomes remains to be determined.

• Dubé JB, Boffa MB, Hegele RA, Koschinsky ML. Lipoprotein(a): more interesting than ever after 50 years. Curr Opin Lipidol. 2012;23:133–40. This is one of a quintet of recent reviews that together comprehensively survey the current landscape of Lp(a) research.PubMedCrossRef

• Kronenberg F, Utermann G. Lipoprotein(a): resurrected by genetics. J Intern Med. 2013;273:6–30. This is one of a quintet of recent reviews that together comprehensively survey the current landscape of Lp(a) research.PubMedCrossRef

• Taleb A, Witztum JL, Tsimikas S. Oxidized phospholipids on apoB-100-containing lipoproteins: a biomarker predicting cardiovascular disease and cardiovascular events. Biomark Med. 2011;5:673–94. This is one of a quintet of recent reviews that together comprehensively survey the current landscape of Lp(a) research.PubMedCrossRef

• Kolski B, Tsimikas S. Emerging therapeutic agents to lower lipoprotein (a) levels. Curr Opin Lipidol. 2012;23:560–68. This is one of a quintet of recent reviews that together comprehensively survey the current landscape of Lp(a) research.PubMedCrossRef

Fless GM, Rolih CA, Scanu AM. Heterogeneity of human plasma lipoprotein (a). Isolation and characterization of the lipoprotein subspecies and their apoproteins. J Biol Chem. 1984;259:11470–8.PubMed

• Tsimikas S, Hall JL. Lipoprotein(a) as a potential causal genetic risk factor of cardiovascular disease. J Am Coll Cardiol. 2012;60:716–21. This is one of a quintet of recent reviews that together comprehensively survey the current landscape of Lp(a) research.PubMedCrossRef

McLean JW, Tomlinson JE, Kuang WJ, et al. cDNA sequence of human apolipoprotein(a) is homologous to plasminogen. Nature. 1987;330:132–7.PubMedCrossRef

Koschinsky ML. Novel insights into Lp(a) physiology and pathogenicity: more questions than answers? Cardiovasc Hematol Disord Drug Targets. 2006;6:267–78.PubMedCrossRef

Gabel BR, Koschinsky ML. Analysis of the proteolytic activity of a recombinant form of apolipoprotein(a). Biochemistry. 1995;34:15777–84.PubMedCrossRef

10.

van der Hoek YY, Wittekoek ME, Beisiegel U, et al. The apolipoprotein(a) kringle IV repeats which differ from the major repeat kringle are present in variably sized isoforms. Hum Mol Genet. 1993;2:361–6.PubMedCrossRef

11.

Lackner C, Cohen JC, Hobbs HH. Molecular definition of the extreme size polymorphism in apolipoprotein(a). Hum Mol Genet. 1993;2:933–40.PubMedCrossRef

12.

Marcovina SM, Hobbs HH, Albers JJ. Relation between number of apolipoprotein(a) kringle 4 repeats and mobility of isoforms in agarose gel: basis for a standardized isoform nomenclature. Clin Chem. 1996;42:436–9.PubMed

13.

Marcovina SM, Albers JJ, Wijsman, et al. Differences in Lp(a) concentrations and apo(a) polymorphs between back and white Americans. J Lipid Res. 1996;37:2569–85.PubMed

14.

Brunner C, Lobentanz EM, Petho-Schramm A, et al. The number of identical kringle IV repeats in apolipoprotein(a) affects its processing and secretion by HepG2 cells. J Biol Chem. 1996;271:32403–10.PubMedCrossRef

15.

Li Y, Luke MM, Shiffman D, Devlin JJ. Genetic variants in the apolipoprotein(a) gene and coronary heart disease. Circ Cardiovasc Genet. 2011;4:565–73.PubMedCrossRef

16.

Chennamsetty I, Claudel T, Kostner KM, et al. Farnesoid X receptor represses hepatic human APOA gene expression. J Clin Invest. 2011;121:3724–34.PubMedCrossRef

17.

Chennamsetty I, Claudel T, Kostner KM, Trauner M, Kostner GM. FGF19 signaling cascade suppresses APOA gene expression. Arterioscler Thromb Vasc Biol. 2012;32:1220–7.PubMedCrossRef

18.

Scanu AM, Bamba R. Nicotinic acid and lipoprotein(a): facts, uncertainties, and clinical considerations. Am J Cardiol. 2008;101:44–7.CrossRef

19.

Chennamsetty I, Kostner KM, Claudel T, et al. Nicotinic acid inhibits hepatic APOA gene expression: studies in humans and in transgenic mice. J Lipid Res. 2012;53:2405–12.PubMedCrossRef

20.

AIM-HIGH Investigators, Boden WE, Probstfield JL, Anderson T, et al. Niacin in patients with low HDL cholesterol levels receiving intensive statin therapy. N Engl J Med. 2011;365:2255–67.PubMedCrossRef

21.

HPS2-THRIVE Collaborative Group. HPS2-THRIVE randomized placebo-controlled trial in 25 673 high-risk patients of ER niacin/laropiprant: trial design, pre-specified muscle and liver outcomes, and reasons for stopping study treatment. Eur Heart J. 2013;34:1279–91.CrossRef

22.

Koschinsky ML, Côté GP, Gabel BR, van der Hoek YY. Identification of the cysteine residue in apolipoprotein(a) that mediates extracellular coupling with apolipoprotein B-100. J Biol Chem. 1993;268:19819–25.PubMed

23.

Bonen DK, Hausman AM, Hadjiagapiou C, Skarosi SF, Davidson NO. Expression of a recombinant apolipoprotein(a) in HepG2 cells. Evidence for intracellular assembly of lipoprotein(a). J Biol Chem. 1997;272:5659–67.PubMedCrossRef

24.

White AL, Lanford RE. Cell surface assembly of lipoprotein(a) in primary cultures of baboon hepatocytes. J Biol Chem. 1994;269:28716–23.PubMed

25.

Becker L, Nesheim ME, Koschinsky ML. Catalysis of covalent Lp(a) assembly: evidence for an extracellular enzyme activity that enhances disulfide bond formation. Biochemistry. 2006;45:9919–28.PubMedCrossRef

26.

• Frischmann ME, Ikewaki K, Trenkwalder E, et al. In vivo stable-isotope kinetic study suggests intracellular assembly of lipoprotein(a). Atherosclerosis. 2012;225:322–7. This is a potentially paradigm shifting work that offers a new and different perspective on Lp(a) biosynthesis.PubMedCrossRef

27.

Rader DJ, Cain W, Ikewaki K, et al. The inverse association of plasma lipoprotein(a) concentrations with apolipoprotein(a) isoform size is not due to differences in Lp(a) catabolism but to differences in production rate. J Clin Invest. 1994;93:2758–63.PubMedCrossRef

28.

Rader DJ, Mann WA, Cain W, et al. The low density lipoprotein receptor is not required for normal catabolism of Lp(a) in humans. J Clin Invest. 1995;95:1403–8.PubMedCrossRef

29.

Koschinsky ML, Marcovina SM. Lipoprotein(a). In: Ballantyne CM, editor. Clinical lipidology: a companion to Braunwald’s heart disease. Philadelphia: Saunders; 2009. p. 130–43.

30.

Takagi H, Umemoto T. Atorvastatin decreases lipoprotein(a): a meta-analysis of randomized trials. Int J Cardiol. 2012;154:183–6.PubMedCrossRef

31.

Deshmukh HA, Colhoun HM, Johnson T, et al. Genome-wide association study of genetic determinants of LDL-c response to atorvastatin therapy: importance of Lp(a). J Lipid Res. 2012;53:1000–11.PubMedCrossRef

32.

• Stein EA, Mellis S, Yancopoulos GD, et al. Effect of a monoclonal antibody to PCSK9 on LDL cholesterol. N Engl J Med. 2012;366:1108–18. This is one of a trio of very recent articles identifying novel Lp(a)-lowering strategies.PubMedCrossRef

33.

Lambert G, Sjouke B, Choque B, Kastelein JJ, Hovingh GK. The PCSK9 decade. J Lipid Res. 2012;53:2515–24.PubMedCrossRef

34.

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.PubMedCrossRef

35.

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.PubMedCrossRef

36.

Konerman M, Kulkarni K, Toth PP, Jones SR. Evidence of dependence of lipoprotein(a) on triglyceride and high-density lipoprotein metabolism. J Clin Lipidol. 2012;6:27–32.PubMedCrossRef

37.

Ganji SH, Kamanna VS, Kashyap ML. Niacin and cholesterol: role in cardiovascular disease (review). J Nutr Biochem. 2003;14:298–305.PubMedCrossRef

38.

Gurakar A, Hoeg JM, Kostner G, Papadopoulos NM, Brewer Jr HB. Levels of lipoprotein Lp(a) decline with neomycin and niacin treatment. Atherosclerosis. 1985;57:293–301.PubMedCrossRef

39.

Kamanna VS, Kashyap ML. Mechanism of action of niacin. Am J Cardiol. 2008;101:20B–6B.PubMedCrossRef

40.

Nordestgaard BG, Chapman MJ, Ray K, et al. Lipoprotein(a) as a cardiovascular risk factor: current status. Eur Heart J. 2010;31:2844–53.PubMedCrossRef

41.

Genest JJ, McNamara JR, Salem DN, Schaefer EJ. Prevalence of risk factors in men with premature coronary heart disease. Am J Cardiol. 1991;67:1185–9.PubMedCrossRef

42.

Brousseau ME, Schaefer EJ, Wolfe ML, et al. Effects of an inhibitor of cholesteryl ester transfer protein on HDL cholesterol. N Engl J Med. 2004;350:1505–15.PubMedCrossRef

43.

Barter PJ, Caulfield M, Eriksson M, et al. Effects of torcetrapib in patients at high risk for coronary events. N Engl J Med. 2007;357:2109–22.PubMedCrossRef

44.

Schwartz GG, Olsson AG, Abt M, et al. Effects of dalcetrapib in patients with a recent acute coronary syndrome. N Engl J Med. 2012;367:2089–99.PubMedCrossRef

45.

Cannon CP, Shah S, Dansky HM, et al. Safety of anacetrapib in patients with or at high risk for coronary heart disease. N Engl J Med. 2010;363:2406–15.PubMedCrossRef

46.

Nicholls SJ, Brewer HB, Kastelein JJ, et al. Effects of the CETP inhibitor evacetrapib administered as monotherapy or in combination with statins on HDL and LDL cholesterol: a randomized controlled trial. JAMA. 2011;306:2099–109.PubMedCrossRef

47.

Cao G, Beyer TP, Zhang Y, et al. Evacetrapib is a novel, potent, and selective inhibitor of cholesteryl ester transfer protein that elevates HDL cholesterol without inducing aldosterone or increasing blood pressure. J Lipid Res. 2011;52:2169–76.PubMedCrossRef

48.

• Visser ME, Witztum JL, Stroes ES, Kastelein JJ. Antisense oligonucleotides for the treatment of dyslipidemia. Eur Heart J. 2012;33:1451–8. This is one of a trio of recent articles identifying novel Lp(a)-lowering strategies.PubMedCrossRef

49.

Jaeger BR, Richter Y, Nagel D, et al. Longitudinal cohort study on the effectiveness of lipid apheresis treatment to reduce high lipoprotein(a) levels and prevent major adverse coronary events. Nat Clin Pract Cardiovasc Med. 2009;6:229–39.PubMedCrossRef

50.

• Safarova MS, Ezhov MV, Afanasieva OI, et al. Effect of specific lipoprotein(a) apheresis on coronary atherosclerosis regression assessed by quantitative coronary angiography. Atheroscler Suppl. 2013;14:93–9. This is one of a trio of recent articles identifying novel Lp(a)-lowering strategies.PubMedCrossRef

51.

Boerwinkle E, Leffert CC, Lin J, et al. Apolipoprotein(a) gene accounts for greater than 90% of the variation in plasma lipoprotein(a) concentrations. J Clin Invest. 1990;90:52–60.CrossRef

52.

Sandholzer C, Boerwinkle E, Saha N, et al. Apolipoprotein(a) phenotypes, Lp(a) concentration and plasma lipid levels in relation to coronary heart disease in a Chinese population: evidence for the role of the apo(a) gene in coronary heart disease. J Clin Invest. 1992;89:1040–6.PubMedCrossRef

53.

Clarke R, Peden JF, Hopewell JC, et al. Genetic variants associated with Lp(a) lipoprotein level and coronary disease. N Engl J Med. 2009;361:2518–28.PubMedCrossRef

54.

Koch W, Mueller JC, Schrempf M, et al. Two rare variants explain association with acute myocardial infarction in an extended genomic region including the apolipoprotein(A) gene. Ann Hum Genet. 2013;77:47–55.PubMedCrossRef

55.

Lv X, Zhang Y, Rao S, et al. Lack of association between four SNPs in the SLC22A3-LPAL2-LPA gene cluster and coronary artery disease in a Chinese Han population: a case control study. Lipids Health Dis. 2012;11:128.PubMedCrossRef

56.

Chasman DI, Shiffman D, Zee RY, et al. Polymorphism in the apolipoprotein(a) gene, plasma lipoprotein(a), cardiovascular disease, and low-dose aspirin therapy. Atherosclerosis. 2009;203:371–6.PubMedCrossRef

57.

Shiffman D, Slawsky K, Fusfeld L, Devlin JJ, Goss TF. Cost-effectiveness model of use of genetic testing as an aid in assessing the likely benefit of aspirin therapy for primary prevention of cardiovascular disease. Clin Ther. 2012;34:1387–94.PubMedCrossRef

58.

Kamstrup PR, Tybjaerg-Hansen A, Steffensen R, Nordestgaard BG. Genetically elevated lipoprotein(a) and increased risk of myocardial infarction. JAMA. 2009;301:2331–9.PubMedCrossRef

59.

Kronenberg F, Kronenberg MF, Kiechl S, et al. Role of lipoprotein(a) and apolipoprotein(a) phenotype in atherogenesis: prospective results from the Bruneck study. Circulation. 1999;100:1154–60.PubMedCrossRef

60.

Paultre F, Pearson TA, Weil HF, et al. High levels of Lp(a) with a small apo(a) isoform are associated with coronary artery disease in African American and White men. Arterioscler Thromb Vasc Biol. 2000;20:2619–24.PubMedCrossRef

61.

Erqou S, Thrompson A, Di Angelantonio E, et al. Apolipoprotein(a) isoforms and the risk of vascular disease. J Am Coll Cardiol. 2010;55:2160–7.PubMedCrossRef

62.

Enkhmaa B, Anuurad E, Zhang W, Tran T, Berglund L. Lipoprotein(a): genotype-phenotype relationship and impact on atherogenic risk. Metab Syndr Relat Disord. 2011;9:411–8.PubMedCrossRef

63.

Gurdasani D, Sjouke B, Tsimikas S, et al. Lipoprotein(a) and risk of coronary, cerebrovascular, and peripheral artery disease: the EPIC-Norfolk prospective population study. Arterioscler Thromb Vasc Biol. 2012;32:3058–65.PubMedCrossRef

64.

Goldenberg NA, Bernard TJ, Hillhouse J, et al. Elevated lipoprotein (a), small apolipoprotein (a), and the risk of arterial ischemic stroke in North American children. Haematologica. 2013;98:802–7.PubMedCrossRef

65.

Ronald J, Rajagopalan R, Cerrato F, et al. Genetic variation in LPAL2, LPA, and PLG predicts plasma lipoprotein(a) level and carotid artery disease risk. Stroke. 2011;42:2–9.PubMedCrossRef

66.

Momiyama Y, Ohmori R, Fayad ZA, et al. Associations between serum lipoprotein(a) levels and the severity of coronary and aortic atherosclerosis. Atherosclerosis. 2012;222:241–4.PubMedCrossRef

67.

Marcovina SM, Koschinsky ML, Albers JJ, Skarlatos S. Report of the National Heart, Lung, and Blood Institute Workshop on Lipoprotein(a) and Cardiovascular Disease: recent advances and future directions. Clin Chem. 2003;49:1785–96.PubMedCrossRef

68.

Brown WV, Ballantyne CM, Jones PH, Marcovina S. Management of Lp(a). J Clin Lipidol. 2010;4:240–7.PubMedCrossRef

69.

• Davidson MH, Ballantyne CM, Jacobson TA, et al. Clinical utility of inflammatory markers and advanced lipoprotein testing: advice from an expert panel of lipid specialists. J Clin Lipidol. 2011;5:338–67. This is a comprehensive work that offers evidence-based advice on the use of Lp(a) in the clinical setting.PubMedCrossRef

70.

Sharrett AR, Ballantyne CM, Coady SA, et al. Coronary heart disease prediction from lipoprotein cholesterol levels, triglycerides, lipoprotein(a), apolipoproteins A-I and B, and HDL density subfractions: the Atherosclerosis Risk in Communities (ARIC) study. Circulation. 2001;104:1108–13.PubMedCrossRef

71.

Emerging Risk Factors Collaboration. Lipid-related markers and cardiovascular disease prediction. JAMA. 2012;307:2499–506.CrossRef

72.

Robinson JG. What is the role of advanced lipoprotein analysis in practice? J Am Coll Cardiol. 2012;60:2607–15.PubMedCrossRef

73.

Boffa MB, Marcovina SM, Koschinsky ML. Lipoprotein(a) as a risk factor for atherosclerosis and thrombosis: mechanistic insights from animal models. Clin Biochem. 2004;37:333–43.PubMedCrossRef

74.

Aznar J, Estellés A, Bretó M, España F, Alós T. Euglobulin clot lysis induced by tissue-type plasminogen activator is reduced in subjects with increased levels of lipoprotein (a). Thromb Res. 1992;66:569–82.PubMedCrossRef

75.

• Kamstrup PR, Tybjærg-Hansen A, Nordestgaard BG. Genetic evidence that lipoprotein(a) associates with atherosclerotic stenosis rather than venous thrombosis. Arterioscler Thromb Vasc Biol. 2012;32:1732–41. This is one of two recent articles that suggest the primary pathogenic mechanism of Lp(a) is promotion of atherosclerosis, not inhibition of fibrinolysis.PubMedCrossRef

76.

• Helgadottir A, Gretarsdottir S, Thorleifsson G, et al. Apolipoprotein(a) genetic sequence variants associated with systemic atherosclerosis and coronary atherosclerotic burden but not with venous thromboembolism. J Am Coll Cardiol. 2012;60:722–9. This is one of two recent articles that suggest the primary pathogenic mechanism of Lp(a) is promotion of atherosclerosis, not inhibition of fibrinolysis.PubMedCrossRef

77.

Bergmark C, Dewan A, Orsoni A, et al. A novel function of lipoprotein [a] as a preferential carrier of oxidized phospholipids in human plasma. J Lipid Res. 2008;49:2230–9.PubMedCrossRef

78.

Tsimikas S, Clopton P, Brilakis ES, et al. Relationship of oxidized phospholipids on apolipoprotein B-100 particles to race/ethnicity, apolipoprotein(a) isoform size, and cardiovascular risk factors: results from the Dallas Heart Study. Circulation. 2009;119:1711–9.PubMedCrossRef

79.

Edelstein C, Pfaffinger D, Hinman J, et al. Lysine-physphatidylcholine adducts in kringle V impart unique immunological and protein pro-inflammatory properties to human apolipoprotein(a). J Biol Chem. 2003;278:52841–7.PubMedCrossRef

80.

Kiechl S, Willeit J, Mayr M, et al. Oxidized phospholipids, lipoprotein(a), lipoprotein-associated phospholipase A2 activity, and 10-year cardiovascular outcomes: prospective results from the Bruneck study. Arterioscler Thromb Vasc Biol. 2007;27:1788–95.PubMedCrossRef

81.

Tsimikas S, Mallat Z, Talmud PJ, et al. Oxidation-specific biomarkers, lipoprotein(a), and risk of fatal and nonfatal coronary events. J Am Coll Cardiol. 2010;56:946–55.PubMedCrossRef

82.

Seimon TA, Nadolski MJ, Liao X, et al. Atherogenic lipids and lipoproteins trigger CD36-TLR2-dependent apoptosis in macrophages undergoing endoplasmic reticulum stress. Cell Metab. 2010;12:467–82.PubMedCrossRef

83.

• van Dijk RA, Kolodgie F, Ravandi A, et al. Differential expression of oxidation-specific epitopes and apolipoprotein(a) in progressing and ruptured human coronary and carotid atherosclerotic lesions. J Lipid Res. 2012;53:2773–90. This is a richly detailed work that links apo(a) and oxidized phospholipids to dangerous developments in advanced atherosclerotic lesions.PubMedCrossRef

84.

Qasim AN, Martin SS, Mehta NN, et al. Lipoprotein(a) is strongly associated with coronary artery calcification in type-2 diabetic women. Int J Cardiol. 2011;150:17–21.PubMedCrossRef

85.

Raggi P, Cooil B, Hadi A, Friede G. Predictors of aortic and coronary artery calcium on a screening electron beam tomographic scan. Am J Cardiol. 2003;91:744–6.PubMedCrossRef

86.

Lee TC, O’Malley PG, Feuerstein I, Taylor AJ. The prevalence and severity of coronary artery calcification on coronary artery computed tomography in black and white subjects. J Am Coll Cardiol. 2003;41:39–44.PubMedCrossRef

87.

Guerra R, Yu Z, Marcovina S, Peshock R, Cohen JC, Hobbs HH. Lipoprotein(a) and apolipoprotein(a) isoforms: no association with coronary artery calcification in the Dallas Heart Study. Circulation. 2005;111:1471–9.PubMedCrossRef

88.

Kullo IJ, Bailey KR, Bielak LF, et al. Lack of association between lipoprotein(a) and coronary artery calcification in the Genetic Epidemiology Network of Arteriopathy (GENOA) study. Mayo Clin Proc. 2004;79:1258–63.PubMedCrossRef

89.

Sun H, Unoki H, Wang X, et al. Lipoprotein(a) enhances advanced atherosclerosis and vascular calcification in WHHL transgenic rabbits expressing human apolipoprotein(a). J Biol Chem. 2002;277:47486–92.PubMedCrossRef

90.

Jug B, Papazian J, Lee R, Budoff MJ. Association of lipoprotein subfractions and coronary artery calcium in patient at intermediate cardiovascular risk. Am J Cardiol. 2013;111:213–8.PubMedCrossRef

91.

Greif M, Arnoldt T, von Ziegler F, et al. Lipoprotein (a) is independently correlated with coronary artery calcification. Eur J Intern Med. 2013;24:75–9.PubMedCrossRef

92.

• Thanassoulis G, Campbell CY, Owens DS, et al. Genetic associations with valvular calcification and aortic stenosis. N Engl J Med. 2013;368:503–12. This very recent work unexpectedly implicates Lp(a) in the development of calcification in nonatherosclerotic aortic valvular disease.PubMedCrossRef

Title: Update on Lipoprotein(a) as a Cardiovascular Risk Factor and Mediator
Authors: Michael B. Boffa
Marlys L. Koschinsky
Publication date: 01-10-2013
Publisher: Springer US
Published in: Current Atherosclerosis Reports / Issue 10/2013
Print ISSN: 1523-3804
Electronic ISSN: 1534-6242
DOI: https://doi.org/10.1007/s11883-013-0360-6

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