ATRA improves endothelial dysfunction in atherosclerotic rabbits by decreasing CAV-1 expression and enhancing eNOS activity

摘要

The aim of the present study was to explore the protective effects and possible mechanisms of all-trans-retinoic acid (ATRA) against atherosclerosis (AS). Rabbits were randomly allocated for standard or high-fat diet with or without ATRA. After 12 weeks, the aortic rings of the rabbits were removed. Endothelium-dependent relaxation (EDR) induced by acetylcholine and non-endothelium-dependent relaxation induced by sodium nitroprusside in the thoracic aorta were evaluated. NO level and eNOS activity were measured according to the protocol of NO and eNOS ELISA kits. The permeability and morphology of the arterial walls were identified by immunofluorescence and H&E staining respectively. The expression of caveolin-1 (CAV-1) and occludin was analyzed using western blotting and immunohistochemistry. The EDR function was significantly reduced in the AS rabbits compared with the normal group, however it was elevated following treatment with ATRA. The eNOS activity and NO level were reduced in the AS group, however were notably increased following oral administration of ATRA. There was an enhancement of endothelial permeability in the AS group compared with the normal group, which decreased following ATRA treatment. Western blot analysis and immunohistochemical analysis identified an increase in occludin expression after treatment with ATRA, in contrast to CAV-1 expression under the same conditions. ATRA is able to ameliorate high-fat-induced AS in rabbits, which is mediated through the activation of eNOS and downregulating CAV-1 expression.