Yue Yongqiang, Ma Ke, Li Zhen, Wang Zhonggao
Department of Endovascular Surgery, The First Affiliated Hospital, Zhengzhou University, Zhengzhou, Henan 450000, PR China.
Department of Endovascular Surgery, The First Affiliated Hospital, Zhengzhou University, Zhengzhou, Henan 450000, PR China.
Biochem Biophys Res Commun. 2018 Jan 8;495(2):2030-2037. doi: 10.1016/j.bbrc.2017.12.059. Epub 2017 Dec 13.
Intimal hyperplasia is the main cause of restenosis after carotid artery injury, and the underlying mechanism involves the proliferation and migration of vascular smooth muscle cells (VSMCs). Angiotensin II Type 1 Receptor-Associated Protein (ATRAP) has been reported to withstand intimal hyperplasia by inhibiting VSMCs proliferation and migration; however, whether the beneficial effect of ATRAP associates with VSMCs apoptosis remains unclarified. We demonstrated that the adenoviral-mediated overexpression of ATRAP induced VSMC apoptosis, alleviating the balloon injury-induced neointima formation in rats. Under the condition of Angiotensin-II stimulation, ATRAP overexpression induced the apoptosis of rat VSMCs by depressing the PI3K-Akt signaling; whereas up-regulation of Akt by PTEN inhibitor abolished the apoptotic death. Thus, ATRAP regulates carotid intimal hyperplasia through controlling the PI3K-Akt signal-mediated VSMCs apoptosis.
内膜增生是颈动脉损伤后再狭窄的主要原因，其潜在机制涉及血管平滑肌细胞（VSMC）的增殖和迁移。据报道，血管紧张素II 1型受体相关蛋白（ATRAP）通过抑制VSMC增殖和迁移来抵抗内膜增生；然而，ATRAP的有益作用是否与VSMC凋亡相关仍不清楚。我们证明，腺病毒介导的ATRAP过表达诱导VSMC凋亡，减轻大鼠球囊损伤诱导的新生内膜形成。在血管紧张素II刺激条件下，ATRAP过表达通过抑制PI3K-Akt信号诱导大鼠VSMC凋亡；而PTEN抑制剂上调Akt可消除凋亡死亡。因此，ATRAP通过控制PI3K-Akt信号介导的VSMC凋亡来调节颈动脉内膜增生。
