Zhou Xue-Liang, Zhu Rong-Rong, Liu Sheng, Xu Hua, Xu Xinping, Wu Qi-Cai, Liu Ji-Chun
Department of Cardiac Surgery, The First Affiliated Hospital, Nanchang University, Nanchang, China.
Department of Obstetrics and Gynecology, Jiangxi Province Hospital of Integrated Traditional, Nanchang, China.
J Cell Biochem. 2018 Aug;119(8):7105-7112. doi: 10.1002/jcb.27032. Epub 2018 May 8.
Currently, the role of Notch signaling during myocardial infarction (MI) remains controversy. In this study we used in vitro and in vivo approaches to investigate the role of Notch signaling in MI. Using cultured human umbilical vein endothelial cells exposed to hypoxia/reoxygenation (H/R), we demonstrated that H/R inhibited the proliferation, VEGF secretion, and tube formation of HUVECs, and these effects were correlated with the inhibition of Notch signaling. Furthermore, these effects were antagonized by overexpression of NICD but aggravated by knockdown of NICD. In addition, in MI model rats we found that heart dysfunction and angiogenesis in model rats was partly improved by NICD overexpression but was aggravated by knockdown of NICD. In conclusion, these data demonstrate that Notch signaling is downregulated in H/R injury in the hearts. Artificial activation of Notch signaling could promote myocardial survival and angiogenesis and improve cardiac function following H/R injury.
目前，Notch信号通路在心肌梗死（MI）中的作用仍存在争议。在本研究中，我们采用体外和体内方法来研究Notch信号通路在心肌梗死中的作用。利用暴露于缺氧/复氧（H/R）的培养人脐静脉内皮细胞（HUVECs），我们证明H/R抑制了HUVECs的增殖、VEGF分泌和管腔形成，并且这些效应与Notch信号通路的抑制相关。此外，这些效应被NICD的过表达所拮抗，但被NICD的敲低所加重。另外，在心肌梗死模型大鼠中，我们发现模型大鼠的心脏功能障碍和血管生成通过NICD的过表达得到部分改善，但被NICD的敲低所加重。总之，这些数据表明在心脏的H/R损伤中Notch信号通路被下调。人工激活Notch信号通路可促进心肌存活和血管生成，并改善H/R损伤后的心脏功能。
