lipid-lowering drugs

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hypolipidemic drugs lipid-lowering drugs what are lipoproteins? lipoproteins are protein-lipid complexes. 2 inner droplet of neutral (water-insoluble core lipids); primarily triglycerides and cholesteryl esters a solubilizing surface layer of phospholipids and unesterified cholesterol specific proteins (apolipoproteins) attached to the outer lipid layer through their specific lipophilic domains the players – lipids triacylglycerol phospholipids cholesterol cholesteryl esters the players - apolipoproteins apo ai (liver, small intestine) structural; activator of lecithin:cholesterol acyltransferase (lcat) apo aii (liver) structural; inhibitor of hepatic lipase; component of ligand for hdl binding apo a-iv (small intestine) activator of lcat; modulator of lipoprotein lipase (lpl) apo a-v (liver) direct functional role is unknown; regulates tg levels. apolipoproteins apo b-100 (liver) structural; synthesis of vldl; ligand for ldl-receptor apo b-48 (small intestine) structural; synthesis of chylomicrons; derived from apo b-100 mrna following specific mrna editing apo e (liver, macrophages, brain) ligand for apoe receptor; mobilization of cellular cholesterol apolipoproteins …

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ein metabolism exogenous/chylomicron pathway (dietary fat) endogenous pathway (lipids synthesized by the liver) hdl metabolism (apolipoprotein transfer, cholesteryl ester transfer, reverse cholesterol transport lipoprotein metabolism exogenous/chylomicron pathway (dietary fat) endogenous pathway (lipids synthesized by the liver) hdl metabolism (apolipoprotein transfer, cholesteryl ester transfer, reverse cholesterol transport surface monolayer phospholipids (12%) free cholesterol (14%) protein (4%) hydrophobic core triglyceride (65%) cholesteryl esters (8%) tg rich: vldl cholesterol and atherosclerosis, grundy) 11 vldl contain 60-70% triglycerides produced by the liver transport endogenously synthesized triglycerides to peripheral tissues vldl metabolism cholesterol and atherosclerosis, grundy) apo c’s and apoe and cholesteryl ester are acquired from hdl in circulation fatty acid transport cholesterol and atherosclerosis, grundy) apoc-ii activates lipoprotein lipase which catalyses the hydrolysis of tg vldl conversion to ldl cholesterol and atherosclerosis, grundy) further action on idl by hepatic lipase loses additional apolipoproteins (apoe) becomes and is converted to ldl surface monolayer phospholipids (25%) …

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rol (7%) protein (45%) hydrophobic core triglyceride (5%) cholesteryl esters (18%) ce rich: hdl cholesterol and atherosclerosis, grundy) 18 smallest of the lipoproteins synthesized by intestine and liver as nascent cholesterol-poor lipoprotein accumulates cholesterol and cholesteryl esters through interactions with peripheral cells and other lipoproteins participates in reverse cholesterol transport, removal of excess cholesterol from peripheral cells and delivery to the liver for metabolism hdl metabolism nascent hdl (lipid-poor apoa-i) is produced by the liver and intestine 19 pathways involved in the generation and conversion of hdl. mature hdl3 and hdl2 are generated from lipid-free apoa-i or lipid-poor pre-ß1-hdl as the precursors. these precursors are produced as nascent hdl by the liver or intestine or are released from lipolysed vldl and chylomicrons or by interconversion of hdl3 and hdl2. abc1-mediated lipid efflux from cells is important for initial lipidation; lcat-mediated esterification of cholesterol generates spherical particles that continue to grow …

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rrows represent lipid transfer processes, and red arrows represent protein transfer processes. tgrl indicates triglyceride-rich lipoproteins hepatic cholesterol metabolism hepatic cholesterol synthesis cholesterol and atherosaclerosis, grundy) rate limiting only pathway for cholesterol degradation energetically expensive; prefer to conserve what is already made/acquired – ldl receptor pathway ldl cellular metabolism cholesterol and atherosaclerosis, grundy) ldl are taken up by the ldl receptor into clathrin-coated pits endothelial dysfunction increased endothelial permeability to lipoproteins and plasma constituents mediated by no, pdgf, ag-ii, endothelin. up-regulation of leukocyte adhesion molecules (l-selectin, integrins, etc). up-regulation of endothelial adhesion molecules (e-selectin, p-selectin, icam-1, vcam-1). migration of leukocytes into artery wall mediated by oxldl, mcp-1, il-8, pdgf, m-csf. ross, nejm; 1999 formation of fatty streak smc migration stimulated by pdgf, fgf-2, tgf-b t-cell activation mediated by tnf-a, il-2, gm-csf. foam-cell formation mediated by oxldl, tnf-a, il-1,and m-csf. platelet adherence and aggregation stimulated by integrins, p-selectin, fibrin, txa2, and …

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age and thrombus formation ross, nejm; 1999 role of ldl in atherosclerosis steinberg d et al. n engl j med 1989;320:915-924. endothelium vessel lumen ldl ldl readily enter the artery wall where they may be modified ldl intima modified ldl modified ldl are proinflammatory hydrolysis of phosphatidylcholine to lysophosphatidylcholine other chemical modifications oxidation of lipids and apob aggregation lipids online 27 role of ldl in inflammation ldl readily enters the artery wall by crossing the endothelial membrane. once in the arterial wall, if ldl accumulates, it is subject to a variety of modifications. the best known of these is oxidation, both of the lipids and of the apo b. ldl is also subject to aggregation, and its phospholipids are subject to hydrolysis by phospholipases to form lysophosphatidylcholine. several other chemical modifications have also been reported. the net effect of these changes is the production of a variety of modified ldl …

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hypolipidemic drugs lipid-lowering drugs what are lipoproteins? lipoproteins are protein-lipid complexes. 2 inner droplet of neutral (water-insoluble core lipids); primarily triglycerides and cholesteryl esters a solubilizing surface layer of phospholipids and unesterified cholesterol specific proteins (apolipoproteins) attached to the outer lipid layer through their specific lipophilic domains the players – lipids triacylglycerol phospholipids cholesterol cholesteryl esters the players - apolipoproteins apo ai (liver, small intestine) structural; activator of lecithin:cholesterol acyltransferase (lcat) apo aii (liver) structural; inhibitor of hepatic lipase; component of ligand for hdl binding apo a-iv (small intestine) activator of lcat; modulator of lipoprotein lipase (lpl) apo a-v (liv...

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