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HDL Cholesterol Protects Endothelial Function

Protection due to efflux of cholesterol from cells

FRIDAY, Oct. 17 (HealthDay News) -- High-density lipoprotein (HDL) cholesterol protects the function of the endothelial cells lining arteries primarily via the ABCG1 protein, which promotes the outflow of cholesterol and related compounds from these cells and may explain why higher plasma HDL levels protect against atherosclerosis, according to a research article published online Oct. 16 in the Journal of Clinical Investigation.

Naoki Terasaka, and colleagues from Columbia University College of Physicians and Surgeons in New York City, examined endothelial cell function in mice lacking the transporters ABCA1 and ABCG1, which promote cholesterol and oxysterol efflux from macrophages, alone or in combination after being fed a high-cholesterol diet or a Western diet.

The researchers report that non-atherosclerotic arteries from mice fed a high-cholesterol diet and lacking ABCG1 alone or in combination showed a marked decrease in endothelium-dependent vasorelaxation, while the effect was milder in mice lacking ABCA1. The investigators found that ABCG1 was primarily expressed in endothelial cells, and endothelial cells from mice lacking ABCG1 and fed a Western diet accumulated the oxysterol 7-ketocholesterol. ABCG1 promoted the efflux of cholesterol and 7-ketocholesterol from human aortic endothelial cells, and treating these cells with HDL prevented the production of reactive oxygen species induced by 7-ketocholesterol in an ABCG1-dependent manner.

The data "suggest that the underlying mechanism by which increased or basal HDL levels protect the endothelium involves efflux of dietary sterols, especially 7-oxysterols from endothelial cells to HDL, mediated principally by ABCG1," Terasaka and colleagues conclude.

A co-author disclosed financial ties to several pharmaceutical companies.

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