hdl代谢生理学和病理学意义.pptVIP

Role of Hepatic Lipase and Lipoprotein Lipase in HDL Metabolism CM = chylomicron; CMR = chylomicron remnant; HDL = high-density lipoprotein; HL = hepatic lipase; IDL = intermediate-density lipoprotein; LPL = lipoprotein lipase; PL = phospholipase; TG = triglyceride B Kidney Endothelium B TG CMR/IDL C-II CM/VLDL HL LPL A-I CE TG HDL2 PL A-I CE HDL3 PL Phospholipids and apolipoproteins Primary (Genetic) Causes of Low HDL-C ApoA-I Complete apoA-I deficiency ApoA-I mutations (eg, ApoA-IMilano) LCAT Complete LCAT deficiency Partial LCAT deficiency (fish-eye disease) ABC1 Tangier disease Homozygous Heterozygous Familial hypoalphalipoproteinemia (some families) Unknown genetic etiology Familial hypoalphalipoproteinemia (most families) Familial combined hyperlipidemia with low HDL-C Metabolic syndrome Complete ApoA-I Deficiency Markedly reduced HDL-C levels and absent apoA-I Cutaneous xanthomas (some patients) Premature atherosclerotic vascular disease (some patients) ApoA-I Mutations Modest to marked reduction in HDL-C and apoA-I Rapid catabolism of apoA-I Systemic amyloidosis Premature atherosclerotic disease (rare) LCAT Deficiency and Fish-eye Disease Both due to mutations in LCAT gene: LCAT deficiency – complete Fish-eye disease – partial Common to both types of LCAT deficiency: Markedly reduced HDL-C and apoA-I levels Rapid catabolism of apoA-I and apoA-II Corneal arcus Premature atherosclerotic vascular disease (rare) Unique to complete LCAT deficiency: Proteinuria and progressive renal insufficiency HDL Metabolism in LCAT Deficiency A-I FC FC LCAT A-I ABC1 Macrophage Rapid catabolism Nascent HDL CE Tangier Disease Autosomal codominant disorder due to mutations in both alleles of ABC1 gene Extremely marked reduction in HDL-C and apoA-I Markedly accelerated catabolism of apoA-I and apoA-II Cholesterol accumulation: Enlarged orange tonsils Hepatosplenomegaly Peripheral neuropathy Tangier Disease(Continued) Increased risk of premature atherosclerotic vascular d