高脂血症治疗目标：高密度脂蛋白课件.pptVIP

HDL as a Therapeutic TargetDaniel J. Rader, M.D. Low HDL-C is an Independent Predictor of CHD Risk Even When LDL-C is Low Low HDL-C was redefined as 40 mg/dL Is HDL-C Simply a Marker of Increased Cardiovascular Risk? Smoke Are sedentary Are obese Are insulin resistant or diabetic Have hypertriglyceridemia Have chronic inflammatory disorders Production of Apo A-I by Liver and Intestine Increased Apo A-I Production is Antiatherogenic in Animals Reduced initiation and progression of atherosclerosis in transgenic mice and rabbits Regression of pre-existing atherosclerosis in animals HDL Metabolism as a Therapeutic Target: Potential Strategies Increase apo A-I production Promote reverse cholesterol transport Delay catabolism of HDL Approaches to Increasing Apo A-I Production Small molecule upregulation of apo A-I gene transcription Intravenous infusion of recombinant protein (wild-type apo A-I, apo A-IMilano) Administration of peptides based on apo A-I sequence Somatic gene transfer of apo A-I DNA (liver, intestine, muscle, hematopoetic cells) HDL as a Therapeutic Target: Potential Strategies Increase apo A-I production Promote reverse cholesterol transport Delay catabolism of HDL HDL and Reverse Cholesterol Transport Regulation of Cholesterol Efflux in the Macrophage Pharmacologic Manipulation of Cholesterol Efflux HDL as a Therapeutic Target: Potential Strategies Increase apo A-I production Promote reverse cholesterol transport Delay catabolism of HDL Mechanisms Other Than Reverse Cholesterol Transport by Which HDL May be Antiatherogenic Antioxidant effects Inhibition of adhesion molecule expression Inhibition of platelet activation Prostacyclin stabilization Promotion of NO production HDL Metabolism: Intravascular Remodeling of HDL HDL Metabolism: Role of Hepatic Lipase HDL Metabolism: Role of CETP HDL Metabolism in CETP Deficiency Inhibition of CETP by JTT-705 in Cholesterol-Fed Rabbits Significantly Reduced Aortic Atherosclerosis HDL Metabolism: In