Effects of bezafibrate and simvastatin on endothelial activation and lipid peroxidation in hypercholesterolemia: evidence of different vascular protection by different lipid-lowering treatments.
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.
Desideri
Giovambattista
G
Department of Internal Medicine and Public Health, University of L'Aquila, 67100 Coppito-L'Aquila, Italy. giovambattista.desideri@cc.univaq.it
Croce
Giuseppe
G
Tucci
Marzia
M
Passacquale
Gabriella
G
Broccoletti
Simona
S
Valeri
Letizia
L
Santucci
Anna
A
Ferri
Claudio
C
D000328:Adult; D000924:Anticholesteremic Agents / Q000008:administration & dosage*; D000975:Antioxidants / Q000008:administration & dosage; D001562:Benzimidazoles / Q000008:administration & dosage*; D015237:Dinoprost / Q000031:analogs & derivatives*; D019040:E-Selectin / Q000378:metabolism; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism; D028441:F2-Isoprostanes / Q000378:metabolism; D005260:Female; D006801:Humans; D006937:Hypercholesterolemia / Q000188:drug therapy* / Q000378:metabolism*; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D019821:Simvastatin / Q000008:administration & dosage*; D012995:Solubility; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism; D014810:Vitamin E / Q000008:administration & dosage
D000924:Anticholesteremic Agents; D000975:Antioxidants; D001562:Benzimidazoles; D019040:E-Selectin; D028441:F2-Isoprostanes; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; D014810:Vitamin E; C075750:8-epi-prostaglandin F2alpha; C004461:bezitramide; D019821:Simvastatin; D015237:Dinoprost