PHYSICOCHEMICAL CHANGES IN HDL3 AFTER BEZAFIBRATE TREATMENT - INFLUENCE ON FREE-CHOLESTEROL EFFLUX FROM HUMAN FIBROBLASTS

The effects of bezafibrate, a well-used fibric acid hypolipidemic agen t, were investigated in 10 moderately hypertriglyceridemic patients. T he aim was to quantify the physico-chemical modifications to high-dens ity lipoprotein subfraction 3 (HDL3) induced by treatment and to asses s, in vitro, the alterations in its principal physiological function, the efflux of intracellular free cholesterol. Treatment (200 mg/thrice /d for 3 months) resulted in a 48% decrease in plasma triglycerides, w ith an increase in the HDL cholesterol, due mainly to an increase in t he HDL3 (P < 0.01). Composition analysis of HDL, indicated an increase in cholesterol esters (P < 0.01), free cholesterol (P < 0.01), and ph ospholipids (P < 0.01), coupled with a decrease in the protein content of the molecule compared with pretreatment values. Fluorescense aniso tropy at 24 degrees C was significantly higher post-treatment than pre treatment (P < 0.01). The cholestrol effluxing capacity of pretreatmen t HDL3 was 28%, and post-treatment this increased to 50% (P < 0.01). M ultivariate analyses indicated that the increased capacity of HDL3 to promote free cholesterol efflux was, in part, due to increased HDL3 ph ospholipid content and a more adequate fluidity of the molecule. These findings suggest that bezafibrate induces a lowering of plasma trigly cerides and that the resultant physico-chemical alterations of the HDL 3 molecule make it more efficient as an acceptor of intracellular free cholesterol.