Journal of Inherited Metabolic Disease

, Volume 26, Issue 2–3, pp 267–287 | Cite as

Lipoprotein disorders and cardiovascular risk

Article

Abstract

Summary: Disorders of lipoproteins often lead to disease in humans. Most often the sequelae of long-term dyslipoproteinaemia lead to atherosclerotic vascular disease in all arterial beds. Plasma elevation of low-density lipoprotein cholesterol (LDL-C), very low-density lipoproteins (VLDL) and lipoprotein(a), and reduced levels of high-density lipoproteins (HDL-C) are risk factors for coronary artery disease. Severe elevations of plasma triglycerides may lead to acute pancreatitis. In Western societies and in emerging economies, lifestyle contributes to the expression of lipoprotein disorders. Many dyslipoproteinaemias have a genetic aetiology. This review will examine the contribution of genetic lipoprotein disorders in human disease. Emphasis will be placed on monogenic disorders that are associated with coronary artery disease and novel causes of disorders of high-density lipoproteins. The consideration of screening and treatment of affected individuals, especially children, must take into account the severity of the phenotype, the long-term risk of developing vascular disease and available evidence of clinical benefit in a group of diseases that are mostly asymptomatic until manifestations of organ ischaemia in the heart, limbs or brain.

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REFERENCES

  1. Acton S, Rigotti A, Landschulz KT, Xu S, Hobbs HH, Krieger M (1996) Identification of scavenger receptor SR-BI as a high density lipoprotein receptor. Science 271: 518-521.PubMedGoogle Scholar
  2. Assmann G, Schulte H, von Eckardstein A, Huang Y (1996) High-density lipoprotein cholesterol as a predictor of coronary heart disease risk. The PROCAM experience and pathophysiological implications for reverse cholesterol transport. Atherosclerosis 124: S11-20.PubMedCrossRefGoogle Scholar
  3. Berge KE, Tian H, Graf GA, et al (2000) Accumulation of dietary cholesterol in sitosterolemia caused by mutations in adjacent ABC transporters. Science 290(5497): 1709 1711.CrossRefGoogle Scholar
  4. Brooks-Wilson A, Marcil M, Clee S, et al (1999) Mutations in the ATP binding cassette (ABC1) transporter gene in Tangier disease and familial HDL deficiency. Nature Genetics 22: 336-345.PubMedCrossRefGoogle Scholar
  5. Brown MS, Brown JL (1997) The SREBP pathway: regulation of cholesterol metabolism by proteolysis of a membrane-bound transcription factor. Cell 89: 331-340.PubMedCrossRefGoogle Scholar
  6. Brown MS, Goldstein JL (1986) A receptor-mediated pathway for cholesterol homeostasis. Science 232: 34-47.PubMedGoogle Scholar
  7. Danesh J, Collins R, Peto R (2000) Lipoprotein (a) and coronary heart disease. Meta-analysis of prospective studies. Circulation 102: 1082-1085.PubMedGoogle Scholar
  8. Davignon J, Genest J Jr (1998) Genetic disorders of lipoproteins. Endocrinol Clin North Am 27: 521-549. CrossRefGoogle Scholar
  9. de Man FH, de Beer F, van der Laarse A, Smelt AH, Havekes LM (1997) Lipolysis of very low density lipoproteins by heparan sulfate proteoglycan-bound lipoprotein lipase. Lipid Res 38(12): 2465 2472.Google Scholar
  10. Emi M, Asaoka H, Matsumoto A, et al (1993) Structure, organization, and chromosomal mapping of the human macrophage scavenger receptor gene. J Biol Chem 268: 2120-2125.PubMedGoogle Scholar
  11. Feoli-Fonseca JC, Levy E, Godard M, Lambert M (1998) Familial lipoprotein lipase deficiency in infancy: clinical, biochemical, and molecular study. J Pediatr 133: 417-423.PubMedCrossRefGoogle Scholar
  12. Genest J (2002) Genetics and prevention: a new look at HDL cholesterol. Cardiol Rev 10: 61-71.PubMedCrossRefGoogle Scholar
  13. Genest J Jr, Martin-Munley SR, McNamara JR, et al (1992) Familial lipoprotein disorders in patients with premature coronary artery disease. Circulation 85: 2025-2033.PubMedGoogle Scholar
  14. Genest JJ, Marcil M, Denis M, et al (1999) High-density lipoproteins in health and in disease. J Invest Med 47: 31-42.Google Scholar
  15. Grundy SM (1997) Small LDL, atherogenic, dyslipidemia, and the metabolic syndrome. Circulation 95: 1-4.PubMedGoogle Scholar
  16. Hansen PS, Defesche JC, Kastelein JJP, et al (1997) Phenotypic variation in patients hetero-zygous for familial defective apolipoprotein B (FDB) in three European countries. Arterioscler Thromb Vasc Biol 17: 741-747.PubMedGoogle Scholar
  17. Havel RJ, Kane JP (1995) Structure and metabolism of plasma lipoproteins. In: Scriver CR, Beaudet AL, Sly WS, Valle D, eds. The Metabolic andMolecular Bases of Inherited Disease, 7th edn. New York: McGraw-Hill, 1841 1851.Google Scholar
  18. Hiltunen TP, Luoma JS, Nikkari T, Yla-Herttuala S (1998) Expression of LDL receptor, VLDL receptor, LDL receptor-related protein, and scavenger receptor in rabbit athe-rosclerotic lesions: marked induction of scavenger receptor and VLDL receptor expression during lesion development. Circulation 97(11): 1079-1086.PubMedGoogle Scholar
  19. Kuivenhoven JA, de Knijff P, Boer JM, et al (1997a) Heterogeneity at the CETP gene locus. Influence on plasma CETP concentrations and HDL cholesterol levels. Arterioscler Thromb Vasc Biol 17(3): 560 568. PubMedGoogle Scholar
  20. Kuivenhoven JA, Pritchard H, Hill J, Frohlich J, Assmann G, Kastelein J (1997b) The molecular pathology of lecithin:cholesterol acyltransferase (LCAT) deficiency syndromes. J Lipid Res 38: 191-205.PubMedGoogle Scholar
  21. Mahley RW, Huang Y, Rall SC Jr (1999) Pathogenesis of type III hyperlipoproteinemia (dysbetalipoproteinemia): questions, quandaries, and paradoxes. J Lipid Res 11: 1933-1949.Google Scholar
  22. Marcil M, Brooks-Wilson A, Clee S, et al (1999) Familial HDL deficiency with defective cholesterol efflux is caused by mutations in cholesterol efflux regulatory protein (CERP/ABC1). Lancet 354: 1341-1346.PubMedCrossRefGoogle Scholar
  23. MRC/BHF Heart Protection Study of cholesterol lowering with simvastatin in 20 536 high-risk individuals: a randomized placebo-controlled trial (2002). Heart Protection Study Collaborative Group. Lancet 360: 7-22.Google Scholar
  24. Murray CJL, Lopez AD (1997) Mortality by cause for eight regions of the world: Global Burden of Disease Study. Lancet 349: 1269-1276.PubMedCrossRefGoogle Scholar
  25. Murray I. Kohl J, Cianflone K (1999) Acylation-stimulating protein (ASP): structure function determinants of cell surface binding and triacylglycerol synthetic activity. Biochem J 342(Pt 1): 41-48.CrossRefGoogle Scholar
  26. Narcisi TME, Shoulders CC, Chester SA, et al (1995) Mutations of the microsomal triglyceride-transfer-protein gene in abetalipoproteinemia. Am JHum Genet 57: 1298-1310.PubMedGoogle Scholar
  27. NCEP (2001) Executive summary of the third report of the National Cholesterol Education Program (NCEP) expert panel on detection, evaluation and treatment of high blood cholesterol in adults (Adults Treatment Panel III) (2001). JAMA 285: 2486-2497.CrossRefGoogle Scholar
  28. O'Connell B, Genest J Jr (2001) High density lipoproteins and endothelial function. Circulation 104: 1978-1983.PubMedGoogle Scholar
  29. Oram JF (2000) Tangier disease and ABCA1. Biochim Biophys Acta 1529: 321-330.PubMedGoogle Scholar
  30. Pajukanta P, Nuotio I, Terwilliger JD, et al (1998) Linkage of familial combined hyperlipidaemia to chromosome lq21 q23. Nature Genetics 18: 369-373.PubMedCrossRefGoogle Scholar
  31. Ridker P, Genest J Jr, Libby P (2000) Plasma lipids and lipoproteins and cardiovascular diseases. In: Libby P, Braunwald E eds. Braunwald's Heart Disease. New York: Saunders; 1010-1039.Google Scholar
  32. Ross R (1999) Atherosclerosis an inflammatory disease. N Engl J Med 340(2): 115-126.PubMedCrossRefGoogle Scholar
  33. Santamarina-Fojo S (1998) The familial chylomicronemia syndrome. Endocrinol Metab Clin North Am 27: 551-567. PubMedCrossRefGoogle Scholar
  34. Segrest JP, Jones MK, Klon AE, et al (1999) A detailed molecular belt model for apolipoprotein A-I in discoidal high density lipoprotein. JBiol Chem 274(45): 31755-31758.CrossRefGoogle Scholar
  35. Sirtori CR, Calabresi L, Franceschini G, et al (2001) Cardiovascular status of carriers of the apolipoprotein A-I milano. The Limone sul Garda study. Circulation 103: 1949-1954.PubMedGoogle Scholar
  36. Sorci-Thomas MG, Thomas MJ (2002) The effects of altered apolipoprotein A-I structure on plasma HDL concentration. Trends Cardiovasc Med 12(3): 121-128.PubMedCrossRefGoogle Scholar
  37. Vance DE, Van den Bosch H (2000) Cholesterol in the year 2000. Biochim Biophys Acta 1529: 1-8. PubMedGoogle Scholar
  38. Viana MB, Giugliani R, Leite VHR, et al (1990) Very low levels of high density lipoprotein cholesterol in four sibs of a family with non-neuropathic Niemann Pick disease and sea-blue histiocytosis. J Med Genet 27: 499-504. PubMedCrossRefGoogle Scholar
  39. Weinstock PH, Bisgaier CL, Aalto-Setala K, et al (1995) Severe hypertriglyceridemia, reduced high density lipoprotein, and neonatal death in lipoprotein lipase knockout mice: mild hypertriglyceridemia with impaired very low density lipoprotein clearance in heterozygotes. J Clin Invest 96: 2555-2568. PubMedCrossRefGoogle Scholar
  40. Wilson DJ, Gahan M, Haddad L, et al (1998) A World Wide Web site for low-density lipoprotein receptor gene mutations in familial hypercholesterolemia: sequence-based, tabular, and direct submission data handling. Am J Cardiol 81: 1509-1511.PubMedCrossRefGoogle Scholar
  41. Wilson PW (1990) High-density lipoprotein, low-density lipoprotein and coronary artery disease Am J Cardiol 66(6): 7A-10A.PubMedCrossRefGoogle Scholar
  42. Yusuf S, Reddy S, Ounpuu O, Anand S (2001) Global burden of cardiovascular diseases. Circulation 104: 2746-2753. PubMedGoogle Scholar
  43. Zhang SH, Reddick RL, Piedrahita JA, Maeda N (1992) Spontaneous hypercholesterolemia and arterial lesions in mice lacking apolipoprotein E. Science 258: 468-471.PubMedGoogle Scholar

Copyright information

© Kluwer Academic Publishers 2003

Authors and Affiliations

  1. 1.Cardiovascular Genetics LaboratoryMcGill University Health Center, Royal Victoria HospitalMontrealCanada

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