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Abstract: S3-10 ROLE OF HEPATIC LIPASE IN HDL METABOLISM AND CAD
- Post-meeting symposia - High Density Lipoproteins Abstract: S3-10 Citation: Atherosclerosis Supplement 2009, Vol. 10, Issue 2
ROLE OF HEPATIC LIPASE IN HDL METABOLISM AND CAD J Brunzell, S Deeb Medicine, University of Washington, Seattle, WA Human hepatic lipase (HL) hydrolyzes triglyceride and phospholipid in HDL leading to smaller HDL for interaction with SRB1. Males or centrally obese individuals have elevated HL activity, decreased HDL2 and increased premature CAD. Women have lower HL activity, less central obesity, higher HDL2 cholesterol and less CAD. This would suggest that low HL activity is associated with less CAD. However, a common HL promoter variation (LIPC -514C to T) is associated with lower HL activity and higher HDL2, but is not associated with lower risk for CAD (Johannsen et al. JCEM, online 12-16-09). This paradox might be explained by the effects of HL on LDL size and density. Individuals with familial hypercholesterolemia typically are not obese, and have normal HL activity, HDL cholesterol and plasma triglyceride; with large, buoyant LDL particles. In FH the LIPC promoter variant associated with low HL activity was associated with increased CAD (Dugi et al. Circulation 2001, page 3057). In this situation the adverse effects on HDL2 particle may offset the potential beneficial change in LDL size which would be absent in FH with large, buoyant LDL particles. With hypertriglyceridemia and central obesity, increased CETP mediated exchange of VLDL triglyceride for cholesteryl ester in LDL and HDL would lead to triglyceride enriched LDL and HDL particles. The associated elevated HL activity would lead to proatherogenic small, dense LDL particles. Treatment to lower HL activity (niacin or statin with colestipol) reverses these changes in LDL and causes regression of coronary stenosis (Zambon et al. Circulation 1999, p 1959). The association, in humans, of HL activity with changes in HDL and LDL particles, and, thus, the subsequent risk for premature, CAD appears to depend on the underlying genetic dyslipidemia. NIH HL 30086
ROLE OF HEPATIC LIPASE IN HDL METABOLISM AND CAD J Brunzell, S Deeb Medicine, University of Washington, Seattle, WA Human hepatic lipase (HL) hydrolyzes triglyceride and phospholipid in HDL leading to smaller HDL for interaction with SRB1. Males or centrally obese individuals have elevated HL activity, decreased HDL2 and increased premature CAD. Women have lower HL activity, less central obesity, higher HDL2 cholesterol and less CAD. This would suggest that low HL activity is associated with less CAD. However, a common HL promoter variation (LIPC -514C to T) is associated with lower HL activity and higher HDL2, but is not associated with lower risk for CAD (Johannsen et al. JCEM, online 12-16-09). This paradox might be explained by the effects of HL on LDL size and density. Individuals with familial hypercholesterolemia typically are not obese, and have normal HL activity, HDL cholesterol and plasma triglyceride; with large, buoyant LDL particles. In FH the LIPC promoter variant associated with low HL activity was associated with increased CAD (Dugi et al. Circulation 2001, page 3057). In this situation the adverse effects on HDL2 particle may offset the potential beneficial change in LDL size which would be absent in FH with large, buoyant LDL particles. With hypertriglyceridemia and central obesity, increased CETP mediated exchange of VLDL triglyceride for cholesteryl ester in LDL and HDL would lead to triglyceride enriched LDL and HDL particles. The associated elevated HL activity would lead to proatherogenic small, dense LDL particles. Treatment to lower HL activity (niacin or statin with colestipol) reverses these changes in LDL and causes regression of coronary stenosis (Zambon et al. Circulation 1999, p 1959). The association, in humans, of HL activity with changes in HDL and LDL particles, and, thus, the subsequent risk for premature, CAD appears to depend on the underlying genetic dyslipidemia. NIH HL 30086