HDL Particle Metabolism in Health and Disease
High density lipoprotein (HDL) cholesterol levels < 40 mg/dl are a significant risk factor for coronary heart disease (CHD). Subjects lacking plasma apolipoprotein (apo) A-I, due to defects in the AI/CIII/AIV gene complex, have marked HDL deficiency, normal levels of other lipoproteins, xanthomas, and markedly premature CHD. Subjects with Tangier disease due to defects in the ATP binding cassette (ABCA1) transporter A1, have defective cellular cholesterol efflux, marked HDL deficiency, only very small pre-beta 1 apoA-I containing HDL which are hypercatabolized, mild hypertriglyceridemia, low levels of low density lipoprotein (LDL) cholesterol, and often have premature CHD. Patients with lecithin:cholesteryl acyl transferase (LCAT) deficiency are unable to esterify their cholesterol. These patients have marked HDL deficiency, only very small pre-beta 1 and small alpha 4 apoA-I containing HDL particles which are hypercatabolized, marked HDL deficiency, and low LDL cholesterol levels. They do not develop premature CHD, but develop marked corneal opacification, anemia, and kidney disease. Common familial disorders associated with low HDL and premature CHD include combined hyperlipidemia, dyslipidemia, and hypoalphalipoproteinemia. In the Decreased HDL is often associated with hypertriglyceridemia, obesity, hyperinsulinemia, and diabetes. Variation at the cholesteryl ester transfer protein (CETP), ABCA1, and lipoprotein lipase (LPL) gene loci play a significant role in modulating HDL cholesterol levels and CHD risk. Marked weight loss can normalize the HDL particle profile because of decreased CETP activity. Statin/niacin combination therapy leads to regression of CHD related to upregulation of ABCA1 and increases in very large alpha 1 apoA-I containing HDL.
Supported by grants from NIH and USDA
- © 2010 by American Heart Association, Inc.