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  • ABCA1 ATP-binding cassette transporter A1
  • ABCG1 ATP-binding cassette transporter G1
  • ACAT Acyl-CoA:cholesterol acyltransferase
  • Apo Apolipoprotein
  • ARH Autosomal recessive hypercholesterolemia
  • CETP Cholesteryl ester transfer protein
  • CHD Coronary heart disease
  • CK Creatine kinase
  • FCH Familial combined hyperlipidemia
  • FFA Free fatty acids
  • FH Familial hypercholesterolemia
  • GPIHDLBP Glycosylphosphatidylinositol-anchored HDL-binding protein
  • HDL High-density lipoproteins
  • HMG-CoA Hydroxymethylglutaryl-CoA
  • IDL intermediate density lipoproteins
  • Idol Inducible degrader of the LDL receptor
  • LCAT Lecithin-cholesterol acyltransferase
  • LDL Low-density lipoproteins
  • LMF1 Lipase maturation factor 1
  • Lp(a) Lipoprotein(a)
  • LPL Lipoprotein lipase
  • LRP-1 LDL receptor-related protein-1
  • MCP-1 Monocyte chemoattractant protein-1
  • NAFLD Nonalcoholic fatty liver disease
  • NASH Nonalcoholic steatohepatitis
  • PCPE-2 Procollagen C-proteinase enhancer-2
  • PCSK9 Proprotein convertase subtilisin/kexin type 9
  • PDGF Platelet-derived growth factor
  • SR-BI Scavenger receptor, class B, type I
  • VLDL Very low density lipoproteins

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The clinical importance of lipoprotein disorders derives chiefly from the role of lipoproteins in atherogenesis and its associated risk of coronary and peripheral vascular disease. The greatly increased risk of acute pancreatitis associated with severe hypertriglyceridemia is an additional indication for intervention. Disordered lipid metabolism is also a critical element in nonalcoholic fatty liver disease. Characterization of dyslipidemia is important for selection of appropriate treatment and may provide clues to underlying primary clinical disorders.

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Atherosclerosis

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Atherosclerosis is the leading cause of death in the United States. Abundant epidemiologic evidence establishes its multifactorial character and indicates that the effects of the multiple risk factors are at least additive. Risk factors include hyperlipidemia, hypertension, smoking, diabetes, physical inactivity, decreased levels of high-density lipoproteins (HDL), hyperhomocysteinemia, and hypercoagulable states. Atheromas are complex lesions containing cellular elements, collagen, and lipids. The progression of the lesion is chiefly attributable to its content of unesterified cholesterol and cholesteryl esters. Cholesterol in the atheroma originates in circulating lipoproteins. Atherogenic lipoproteins include low-density (LDL), intermediate density (IDL), very low density lipoproteins (VLDL), and Lp(a) species, all of which contain the B-100 apolipoprotein (Apo B-100). Chylomicron remnants containing apoB-48 are also atherogenic. All of these are subject to oxidation by reactive oxygen species in the tissues and also by lipoxygenases secreted by macrophages in atheromas. Oxidized lipoproteins cause impairment of endothelial cell-mediated vasodilation and stimulate endothelium to secrete monocyte chemoattractant protein-1 (MCP-1) and adhesion molecules that recruit monocytes to the lesion. Tocopherols (vitamin E) are natural antioxidants that localize in the surface monolayers of lipoproteins, exerting resistance to oxidation. Increased oxidative stress such as that induced by smoking depletes the tocopherol content. Oxidation of lipoproteins stimulates their endocytosis via scavenger receptors on macrophages and smooth muscle cells, leading to the formation of foam cells. Recent studies strongly support a role of vitamin D in prevention of atherosclerosis, probably by influencing inflammatory activity of macrophages.

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Hypertension increases access of lipoproteins to the subintima. Smoking accelerates atherogenesis by reducing HDL and increasing thrombogenesis by platelets—in addition to its pro-oxidant effect. Activated platelets release platelet-derived growth factor (PDGF), stimulating proliferation and migration of cells of smooth muscle origin into the lesion.

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