The mechanism of all-trans retinoic acid in the regulation of apelin expression in vascular endothelial cells

Abstract

The apelin gene can promote vascular endothelial cell (VEC) proliferation, migration, and angiogenesis. However, the molecular mechanism for regulation of the apelin gene is still unknown. Real-time PCR and Western blotting analysis were employed to detect the effect of all-trans retinoic acid (ATRA) in up-regulating apelin expression in human umbilical vein endothelial cells (HUVECs). Furthermore, the in vivo study also indicated that ATRA could increase apelin expression in balloon-injured arteries of rats, which is consistent with the results from the cultured HUVECs. To ensure whether retinoic acid receptor (RAR) α (RARα) could be induced by ATRA in regulating apelin, the expression of RARα was tested with a siRNA method to knock down RARα or adenovirus vector infection to overexpress RARα. The results showed that ATRA could up-regulate apelin expression time- and dose- dependently in HUVECs. ATRA could induce a RARα increase; however, the expression of RARβ and RARγ were unchanged. The blocking of RARα signaling reduced the response of apelin to ATRA when HUVECs were treated with RARα antagonists (Ro 41-5253) or the use of siRNA against RARα (si-RARα) knockdown RARα expression before using ATRA. In addition, induction of RARα overexpression by infection with pAd-GFP-RARα further increased the induction of apelin by ATRA. These results suggested that ATRA up-regulated apelin expression by promoting RARα signaling.

Phytoestrogenic Effects of Blackcurrant Anthocyanins Increased Endothelial Nitric Oxide Synthase (eNOS) Expression in Human Endothelial Cells and Ovariectomized Rats

“…Retinoids such as tretinoin are important regulators of cell division and proliferation. Its cosmetic effects on the skin are well known, and several studies have demonstrated the effects of tretinoin on blood vessels [43,44,45]. The current results suggest that BCE may exert an effect similar to that of tretinoin on HUVECs.…”

All-trans retinoic acid has renoprotective effects on Cisplatin-induced acute kidney injury in rats.

“…The results are also in agreement with previous studies reported that injection of cisplatin is accompanied with a significant elevation of MDA content and a marked depletion in GSH content as well as SOD and CAT activities [30]. ATRA is known to have free radical scavenger effects [31], which explain the present results that found that administration of ATRA attenuated the effects of ROS through the decreasing of MDA content and increasing of GSH and CAT activities.…”

Vascular effects of apelin: Mechanisms and therapeutic potential

“…Hypoxia increases apelin gene expression in cultured human pulmonary arterial endothelial and smooth muscle cells via hypoxia inducible factor–1α (HIF-1α) dependent mechanism (Eyries, et al, 2008). Activation of α-retinoic acid receptors by all-trans retinoic acid increases apelin gene expression in HUVEC cells and in carotid arteries from balloon-injured rats (Shi, et al, 2017). Although these studies provide insight into several key pathways involved in apelin regulation, the association between apelin gene expression and release of apelin into the circulation and/or surrounding tissues remains poorly understood.…”