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 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 (200 mg/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 HDL3 indicated 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. Fluorescence anisotropy at 24 degrees 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.
La Ville
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AE
Unitat de Recerca de Lípids i Arteriosclerosi, Facultat de Medicina de Reus, Universitat Rovira i Virgili, Spain.
Solà
R
R
Motta
C
C
Plana
N
N
Heras
M
M
Ribalta
J
J
Masana
L
L
D000328:Adult; D001629:Bezafibrate / Q000627:therapeutic use*; D002478:Cells, Cultured; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D015228:Hypertriglyceridemia / Q000188:drug therapy*; D000960:Hypolipidemic Agents / Q000627:therapeutic use*; D008074:Lipoproteins / Q000097:blood; D008075:Lipoproteins, HDL / Q000378:metabolism*; D053440:Lipoproteins, HDL3; D008297:Male; D008875:Middle Aged; D012867:Skin / Q000187:drug effects* / Q000378:metabolism
D000960:Hypolipidemic Agents; D008074:Lipoproteins; D008075:Lipoproteins, HDL; D053440:Lipoproteins, HDL3; D001629:Bezafibrate