Suppression of vascular cell adhesion molecule-1 expression by crocetin contributes to attenuation of atherosclerosis in hypercholesterolemic rabbits.

Abstract:

:To elucidate the molecular mechanism by which antioxidants alleviate atherosclerosis, we investigated the effect of crocetin, a naturally occurred carotinoid with potent antioxidant power, on vascular cell adhesion molecule-1 (VCAM-1) expression in atherosclerotic rabbits. Twenty-four male New Zealand White rabbits were allocated to three groups fed on standard diet (control group), high lipid diet (HLD group) or high lipid diet supplemented with crocetin (crocetin group), respectively. After 8 weeks of treatment, rabbits in HLD group developed severe hypercholesterolemia and atherosclerosis in aortas, together with a significantly up-regulated expression of both protein and mRNA for VCAM-1. In contrast, supplementation with crocetin resulted in markedly ameliorated atherosclerosis, coupled with a significantly decreased VCAM-1 expression, though plasma lipids level remained comparable to that of HLD group. Regression analysis revealed a positive correlation between VCAM-1 expression and the extent of atherosclerosis (P < 0.01). In addition, immunohistochemical analysis showed an increased activation of nuclear factor kappa B (NF-kappaB), a redox sensitive transcription factor essential for VCAM-1 expression, in aortas from rabbits fed on high lipid diet, which was evidently suppressed by crocetin supplementation. These findings suggest that the antiatherosclerotic effect of crocetin might be attributed, at least in part, to the suppressed expression of VCAM-1, which might result from reduced NF-kappaB activation. This study provides a further insight into the molecular mechanism by which antioxidants attenuate atherosclerosis and suggests a potential target for the treatment of atherosclerosis with antioxidants.

journal_name

Biochem Pharmacol

journal_title

Biochemical pharmacology

authors

Zheng S,Qian Z,Tang F,Sheng L

doi

10.1016/j.bcp.2005.07.034

subject

Has Abstract

pub_date

2005-10-15 00:00:00

pages

1192-9

issue

8

eissn

0006-2952

issn

1873-2968

pii

S0006-2952(05)00490-9

journal_volume

70

pub_type

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