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[Clinical, epidemiologic, and biochemical findings on the reverse cholesterol transport (cholesterol-HDL)]
1Service de Diabétologie-Endocrinologie, Hôpital Pasteur-06002 Nice.
Insights
High-density lipoprotein cholesterol (HDL-C) plays a crucial role in preventing coronary heart disease (CHD) by removing cholesterol. Increasing HDL-C levels, alongside lowering triglycerides, significantly reduces CHD incidence.
Area of Science:
- Cardiovascular Science
- Lipid Metabolism
- Genetic Dyslipidemia
Context:
- High plasma levels of low-density lipoprotein cholesterol (LDL-C) are linked to coronary heart disease (CHD).
- High-density lipoprotein cholesterol (HDL-C) has an antiatherogenic role via reverse cholesterol transport.
- Tangier disease, a rare genetic dyslipidemia with very low HDL-C, offers insights into cholesterol metabolism.
Purpose:
- To elucidate the role of HDL-C in preventing atherosclerosis.
- To understand the pathophysiology of Tangier disease and its impact on cholesterol efflux.
- To highlight the clinical significance of HDL-C levels in coronary patients.
Summary:
- Mutations in ATP-binding cassette transporters reduce cholesterol efflux in Tangier disease, decreasing reverse cholesterol transport.
- Low HDL-C levels are observed in 15-30% of coronary patients, often with high triglycerides, particularly in diabetics.
- HDL-C is an inverse predictor of CHD, with studies showing pharmacological increases reduce CHD incidence.
Impact:
- Low HDL-C levels are a significant risk factor for premature coronary heart disease.
- Targeting HDL-C and triglycerides pharmacologically shows promise in reducing CHD incidence.
- Understanding cholesterol transport mechanisms is vital for developing novel cardiovascular therapies.
Abstract:
Contrary to high plasma levels of low-density lipoprotein cholesterol (LDL-C), closely linked with coronary heart disease (CHD), high-density lipoprotein cholesterol (HDL-C) play an antiatherogenic role, through the reverse cholesterol transport from peripheral cells to the liver. New data in the pathophysiology of a rare genetic dyslipidemia, the Tangier disease, characterized by very low HDL-C levels and premature CHD, have shed light on this complex mechanism. In this disease, cholesterol efflux from peripheral cells is dramatically reduced, and this has been recently shown to be caused by mutations in an ATP-binding cassette transporter, which normally stimulates cholesterol efflux. Reverse cholesterol transport is therefore greatly decreased. Epidemiological data have revealed that 15% to 30% of coronary patients have low HDL-C levels. However, this is often combined with high triglycerides levels, and this association is frequently found in diabetic patients, especially prone to CHD. HDL-C has been repeatedly shown to be an inverse predictor of CHD. This has been enhanced by recent interventional studies (Veterans Affairs HDL Intervention Study, Bezafibrate Infarction Prevention Study) which have provided strong evidence that pharmacological increase of HDL-C, in combination with decrease in triglycerides level, reduces incidence of CHD.