Lipoprotein disorders and cardiovascular risk
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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.
KeywordsCholesteryl Ester Microsomal Triglyceride Transfer Protein Familial Hypercholesterolaemia Cholesterol Ester Transfer Protein Acylation Stimulate Protein
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- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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