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

Abstract

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.

SIRT1 as a potential key regulator for mediating apoptosis in oropharyngeal cancer using cyclophosphamide and all-trans retinoic acid

“…Moreover, ET-1 stimulates VEGF production, which in turn induces endothelial cell proliferation 57 . The combined regimen significantly inhibited ET-1 level, which goes in line with results of Zhang et al 58 and Tao et al 59 . Thereby, CTX and ATRA can be regarded effective in inhibiting angiogenesis in NO3 cell line through significant inhibition of ET-1 and VEGF.…”

Potential Therapeutic Effect of All-Trans Retinoic Acid on Atherosclerosis

“…In addition, ATRA can inhibit the expression of endothelin-1 (ET-1) mRNA in endothelin-1 (ET-1) mRNA in endothelial cells (ECs), leading to anti-atherosclerosis effects [ 125 , 126 ]. ATRA may alleviate atherosclerosis by reducing ET-1 expression and caveolin-1 (CAV-1) expression in atherosclerotic rabbits and increasing endothelial nitric oxide synthase (eNOS) phosphorylation [ 127 , 128 ].…”

The Use of Nutraceuticals to Counteract Atherosclerosis: The Role of the Notch Pathway

“…Peculiarly, in the same animal model, vitamin A deficiency stimulates atherogenesis, prevented by β-carotene supplementation [139]. All-trans retinoic acid (ATRA), a derivative of vitamin A, has been recently shown to reduce the plaque size in a rabbit model of HFD-induced atherosclerosis by inhibiting platelet aggregation, by decreasing caveolin-1 expression and ET-1 secretion and by enhancing eNOS activity and NO formation [140][141][142][143].…”