Effects of bezafibrate and simvastatin on endothelial activation and lipid peroxidation in hypercholesterolemia: evidence of different vascular protection by different lipid-lowering treatments.

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Desideri G, Croce G, Tucci M, Passacquale G, Broccoletti S, Valeri L, Santucci A, Ferri C

Effects of bezafibrate and simvastatin on endothelial activation and lipid peroxidation in hypercholesterolemia: evidence of different vascular protection by different lipid-lowering treatments.

J Clin Endocrinol Metab. 2003 Nov;88(11):5341-7.

PubMed ID

14602771 [ View in PubMed

]

Abstract

Hypercholesterolemia is combined with enhanced lipid peroxidation, which can promote atherogenesis by inducing endothelial adhesion molecule expression. Statins may protect vascular endothelium in hypercholesterolemia by reducing enhanced plasma levels of low-density lipoprotein and decreasing oxidative stress. Herein, we describe increased circulating levels of soluble intercellular adhesion molecule-1, vascular cell adhesion molecule-1, and E-selectin and total 8-iso-prostaglandin F(2 alpha) (8-iso-PGF(2 alpha)) concentrations, as indexes of endothelial activation and lipid peroxidation, respectively, in 67 hypercholesterolemic patients compared with 32 normocholesterolemic subjects. Significant cholesterol reductions were achieved in hypercholesterolemic patients after 6 months under either simvastatin (40 mg/d) or bezafibrate (800 mg/d) treatment, given according to a randomized double-blind trial. Simvastatin but not bezafibrate simultaneously reduced soluble adhesin and total 8-iso-PGF(2 alpha) concentrations also. Vitamin E supplementation (400 IU/d) further reduced indexes of endothelial activation and lipid peroxidation in simvastatin-treated patients and significantly reduced the above indexes in bezafibrate-treated patients. Changes in circulating soluble adhesion molecule levels were directly correlated with changes in total 8-iso-PGF(2 alpha) concentrations in simvastatin-treated patients also receiving vitamin E supplementation. All together, our data demonstrated that hypercholesterolemia was combined with endothelial activation and lipid peroxidation, which were efficaciously counteracted by simvastatin but not bezafibrate treatment. Thus, a different vascular protection can be achieved by different lipid-lowering treatments.

DrugBank Data that Cites this Article

Pharmaco-metabolomics

Drug	Drug Groups	Metabolite	Change	Description
Simvastatin	Approved	8-iso-PGF2α	decreased	Simvastatin decreases the level of 8-iso-PGF2α in the blood
Simvastatin	Approved	LDL cholesterol	decreased	Simvastatin decreases the level of LDL cholesterol in the blood

Pharmaco-proteomics

Drug	Drug Groups	Gene	Gene ID	Change	Interaction	Chromosome
Simvastatin	Approved	ICAM1	3383	decreased	Simvastatin results in decreased expression of ICAM1 protein modified form	19p13.2
Simvastatin	Approved	SELE	6401	decreased	Simvastatin results in decreased expression of SELE protein modified form	1q24.2
Simvastatin	Approved	VCAM1	7412	decreased	Simvastatin results in decreased expression of VCAM1 protein modified form	1p21.2