Bezafibrate and Lovastatin Decrease the Oxidizability of Low-Density Lipoproteins in Heart Transplant Recipients with Hyperlipemia

Abstract

Background Coronary atherosclerotic disease in the graft is a major cause of heart transplant failure.1,2 In these patients, there is an abnormality in lipoprotein metabolism, in part attributable to immunosuppressive therapy.3,4 Oxidized low-density lipoprotein (LDL) plays an important role in the development of atheromas, and recently Apanay et al showed that cyclosporine has an "in vivo" prooxidant effect on plasma LDL. Previous studies have observed a lower plasma level of vitamin E7 (a major endogenous lipid-soluble antioxidant) in heart transplant recipients and increased levels of some indicators of lipid peroxidation.8 This suggests that in these patients oxidized LDL could play a role in the pathogenesis of accelerated coronary artery atherosclerosis. Both bezafibrate and lovastatin have been shown to reduce lipid levels through different mechanisms. Lovastatin, but not bezafibrate, increases the LDL fractional catabolic rate in vivo enhancing the uptake and clearance of this particle by its high affinity receptors. On the other hand, bezafibrate decreases very low density lipoprotein triglyceride plasma levels as a result of a stimulating effect on lipoprotein lipase activity, which could result in an accelerated catabolism of triglyceride-rich lipoproteins.9,10 Previous studies have shown that both drugs are safe, effective, and well-tolerated therapies for hyperlipidemia in heart transplant recipients.11,12 In this study, we evaluated in heart transplant recipients with hyperlipidemia the effect of two lipid-lowering drugs with different mechanisms of action, bezafibrate and lovastatin, on the susceptibility of LDL for oxidation in vitro.

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