Physicochemical Changes in HDL3 after Bezafibrate Treatment: Influence on Free Cholesterol Efflux from Human Fibroblasts

Authors: La Ville, Agnes; Solà, Rosa; Motta, Claude; Plana, Núria; Heras, Mercedes; Ribalta, Josep; Masana, Lluís

Source: Cardiovascular Drugs and Therapy, Volume 11, Number 5, November 1997 , pp. 653-658(6)

Publisher: Springer

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Abstract:

The effects of bezafibrate, a well-used fibric acid hypolipidemic agent, were investigated in 10 moderately hypertriglyceridemic patients. The aim was to quantify the physico-chemical modifications to high-density lipoprotein subfraction 3 (HDL3) induced by treatment and to assess, in vitro, the alterations in its principal physiological function, the efflux of intracellular free cholesterol. Treatment (200mg/thrice/d for 3 months) resulted in a 48% decrease in plasma triglycerides, with an increase in the HDL cholesterol, due mainly to an increase in the HDL3 (P < 0.01). Composition analysis of HDL3indicated an increase in cholesterol esters (P < 0.01), free cholesterol (P < 0.01), and phospholipids (P < 0.01), coupled with a decrease in the protein content of the molecule compared with pretreatment values. Fluorescense anisotropy at 24°C was significantly higher post-treatment than pretreatment (P < 0.01). The cholesterol effluxing capacity of pretreatment HDL3 was 28%, and post-treatment this increased to 50% (P < 0.01). Multivariate analyses indicated that the increased capacity of HDL3 to promote free cholesterol efflux was, in part, due to increased HDL3 phospholipid content and a more adequate fluidity of the molecule. These findings suggest that bezafibrate induces a lowering of plasma triglycerides and that the resultant physico-chemical alterations of the HDL3 molecule make it more efficient as an acceptor of intracellular free cholesterol.

Keywords: bezafibrate; hypertriglyceridemia; HDL3 composition; free cholesterol efflux

Document Type: Research article

DOI: 10.1023/A:1007734924101

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