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

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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.

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Authors and Affiliations

  1. Unitat de Recerca de Lípids i Arteriosclerosi, Unitat Clínico-Experimental Hospital Universitari de Sant Joan, Facultat de Medicina de Reus, Universitat Rovira i Virgili, Spain

    Agnes E. La Ville, Rosa Solà, Núria Plana, Mercedes Heras, Josep Ribalta & Lluís Masana

  2. Laboratoire de Biochimie, Hôtel Dieu, Clermont-Ferrand, France

    Claude Motta

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  1. Agnes E. La Ville
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  2. Rosa Solà
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  3. Claude Motta
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  4. Núria Plana
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  5. Mercedes Heras
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  6. Josep Ribalta
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  7. Lluís Masana
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La Ville, A.E., Solà, R., Motta, C. et al. Physicochemical Changes in HDL3 after Bezafibrate Treatment: Influence on Free Cholesterol Efflux from Human Fibroblasts. Cardiovasc Drugs Ther 11, 653–658 (1997). https://doi.org/10.1023/A:1007734924101

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