Hypoxia inhibits pulmonary artery endothelial cell apoptosis via the e-selectin/biliverdin reductase pathway

• Published in: Microvascular research 2016-07, Vol.106, p.44-56
• Main Authors: Song, Shasha, Yi, Zhi, Zhang, Min, Mao, Min, Fu, Li, Zhao, Xijuan, Liu, Zizhen, Gao, Jiayin, Cao, Weiwei, Liu, Yumei, Shi, Hengyuan, Zhu, Daling
• Format: Article
• Language: English
• Subjects: Animals; Apoptosis; Apoptosis Regulatory Proteins - metabolism; Biliverdin reductase; Cattle; Cells, Cultured; Disease Models, Animal; e-selectin; E-Selectin - genetics; E-Selectin - metabolism; Endothelial Cells - enzymology; Endothelial Cells - pathology; Hypoxia; Hypoxia - enzymology; Hypoxia - pathology; Male; Membrane Potential, Mitochondrial; Mitochondria - metabolism; Mitochondria - pathology; Oxidoreductases Acting on CH-CH Group Donors - genetics; Oxidoreductases Acting on CH-CH Group Donors - metabolism; Pulmonary Artery - enzymology; Pulmonary Artery - pathology; Pulmonary artery endothelial cells; Rats, Wistar; RNA Interference; Signal Transduction; Time Factors; Transfection; Up-Regulation
• ISSN: 0026-2862; 1095-9319
• DOI: 10.1016/j.mvr.2016.03.009

Hypoxia-induced inhibition of apoptosis in pulmonary artery endothelial cells (PAECs) has an important role in pulmonary arterial remodeling leading to aggravated hypoxic pulmonary arterial hypertension. However, the mechanisms involved in the hypoxia-induced inhibition of PAEC apoptosis have not been elucidated. e-selectin and biliverdin reductase (BVR) have been reported to contribute to the cascade of apoptosis in several cell lines but not in PAECs. In the present study, we show that the expression of e-selectin and BVR was both up-regulated by hypoxia in PAECs. Moreover, hypoxia attenuated the decreased cell survival and apoptotic protein expression, and increased DNA fragmentation induced by serum deprivation in the PAECs, which was mediated by the e-selectin/BVR pathway. In addition, by examining the mitochondrial membrane potential and mitochondrial membrane proteins (Bcl-2 and BAX), we show that the mitochondrial-dependent apoptosis pathway was necessary for the e-selectin/BVR pathway inducing the anti-apoptotic effect of hypoxia in PAECs. Taken all together, our data show that the e-selectin/BVR pathway participates in the inhibitory process of hypoxia in PAEC apoptosis which is mediated by the mitochondrial-dependent apoptosis pathway. •Hypoxia increases the expression of e-selectin and BVR in PAECs.•e-selectin/BVR pathway mediates the anti-apoptotic effect of hypoxia on PAECs.•e-selectin/BVR induces hypoxia-inhibited PAECs apoptosis via intrinsic pathway.