VSMC-specific EP4 deletion exacerbates angiotensin II-induced aortic dissection by increasing vascular inflammation and blood pressure

著者: Hu Xu, Shengnan Du, Bingying Fang, Chaojie Li, Xiao Jia, Senfeng Zheng, Sailun Wang, Qingwei Li, Wen Su, Nanping Wang, Feng Zheng, Lihong Chen, Xiaoyan Zhang, Jan-Ακε Gustafsson, Youfei Guan - Proceedings of the National Academy of Sciences, PNAS 2019 被引用: 113

mice exhibited higher blood pressure under basal and AngII-infused conditions. Ex vivo and in vitro studies further revealed that VSMC-specific EP4 gene deficiency significantly increased AngII-elicited vasoconstriction of the mesenteric artery, likely by stimulating intracellular calcium release in VSMCs. Furthermore, EP4 gene ablation and EP4 blockade in cultured VSMCs were associated with a significant increase in MCP-1 and NOX1 expression and a marked reduction in α-SM actin (α-SMA), SM22α, and SM differentiation marker genes myosin heavy chain (SMMHC) levels and serum response factor (SRF) transcriptional activity. To summarize, the present study demonstrates that VSMC EP4 is critical for vascular homeostasis, and its dysfunction exacerbates AngII-induced pathological vascular remodeling. EP4 may therefore represent a potential therapeutic target for the treatment of AD.