• Wenyu Li, Pengfei Xu, Lingqi Kong, Shuo Feng, Nan Shen, Hongmei Huang, Wuxuan Wang, Xiang Xu, Xinyue Wang, Guoping Wang, Yan Zhang, Wen Sun, Wei Hu, and Xinfeng Liu.
• Department of Neurology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, 230001, China.
• Transl Res. 2023 Jul 1; 257: 789278-92.

AbstractAngiogenesis helps to improve neurological recovery by repairing damaged brain tissue and restoring cerebral blood flow (CBF). The role of the Elabela (ELA)-Apelin receptor (APJ) system in angiogenesis has gained much attention. We aimed to investigate the function of endothelial ELA on post-ischemic cerebral angiogenesis. Here, we demonstrated that the endothelial ELA expression was upregulated in the ischemic brain and treatment with ELA-32 mitigated brain injury and enhanced the restoration of CBF and newly formed functional vessels following cerebral ischemia/reperfusion (I/R) injury. Furthermore, ELA-32 incubation potentiated proliferation, migration, and tube formation abilities of the mouse brain endothelial cells (bEnd.3 cells) under oxygen-glucose deprivation/reoxygenation (OGD/R) condition. RNA sequencing analysis indicated that ELA-32 incubation had a role in the Hippo signaling pathway, and improved angiogenesis-related gene expression in OGD/R-exposed bEnd.3 cells. Mechanistically, we depicted that ELA could bind to APJ and subsequently activate YAP/TAZ signaling pathway. Silence of APJ or pharmacological blockade of YAP abolished the pro-angiogenesis effects of ELA-32. Together, these findings highlight the ELA-APJ axis as a potential therapeutic strategy for ischemic stroke by showing how activation of this pathway promotes post-stroke angiogenesis.Copyright © 2023 Elsevier Inc. All rights reserved.

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