HDL代谢的生理学和病理学意义.ppt

HDL and Coronary Heart Disease Physiology and Pathophysiology of HDL Metabolism Structure of HDL Particle Production of HDL by Liver and Intestine HDL Metabolism and Reverse Cholesterol Transport Role of CETP in HDL Metabolism Role of Hepatic Lipase and Lipoprotein Lipase in HDL Metabolism 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 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 disease Pathologic accumulation of cholesterol in macrophages and other cells of reticulo-endothelial system Heterozygotes have moderately reduced HDL-C and apoA-I l