All-trans retinoic acid reduces endothelin-1 expression and increases endothelial nitric oxide synthase phosphorylation in rabbits with atherosclerosis

All-trans retinoic acid (ATRA) is a natural derivative of vitamin A that ameliorates atherosclerosis (AS) by regulating inflammatory factors. However, studies concerning the role of retinoic acid in artery endothelial function are rare. Therefore, the present study investigated its role in regulating the production of endothelin-1 (ET-1) and nitric oxide (NO) in rabbits with AS. The rabbits were randomly divided into 3 groups: The control group was administered an ordinary diet, while the high fat group and the ATRA drug intervention group were administered a high fat diet. After 12 weeks, the blood lipid levels of rabbits, the morphological structure of the arterial wall, the arterial intimal permeability, the activity of blood endothelial nitric oxide synthase (eNOS) and the level of plasma NO were investigated. Western blot analysis was used to detect the levels of ET-1, eNOS and eNOS phosphorylation at Ser-1177 (p-eNOS), and a radioimmunoassay was performed to detect the level of ET-1 in the plasma. It was identified that plaque formation was alleviated in the ATRA group compared with the high fat group, as revealed by hematoxylin and eosin and oil red O staining, and a similar trend was reflected in the immunofluorescence results for endothelial permeability. Western blotting demonstrated significantly decreased ET-1 expression levels in the arterial tissue of rabbits in the ATRA group compared with the high fat group, together with increased p-eNOS level (P< 0.05), however, no difference was observed in the expression of eNOS (P> 0.05). The trends observed for ET-1 and the activity of eNOS in plasma were similar to those for arterial tissue. Therefore, the present study demonstrated that ATRA may regulate the grade of AS by the reduction of ET-1 secretion and increased NO formation via increased phosphorylation of eNOS. ATRA provides a potential novel method for the treatment of atherosclerosis.