Department of Anesthesiology, Affiliated Hospital of Guangdong Medical University, Zhanjiang, China.
Guangdong Key Laboratory of Age-related Cardiac-cerebral Vascular Disease, Institute of Neurology, Affiliated Hospital of Guangdong Medical University, Guangdong Medical University, Zhanjiang, Guangdong, China.
PLoS One. 2018 Jul 11;13(7):e0199373. doi: 10.1371/journal.pone.0199373. eCollection 2018.
Angiotensin II (AngII), a vasoactive peptide that elevates arterial blood pressure and results in hypertension, has been reported to directly induce vascular endothelial cell apoptosis. Recent work has demonstrated that propofol pre-treatment attenuates angiotensin II-induced apoptosis in human coronary artery endothelial cells. However, the underlying mechanism remains largely unknown. Here, we investigated human umbilical vein endothelial cells (HUVECs) subjected to angiotensin II-induced apoptosis in the presence or absence of propofol treatment and found that angiotensin II-induced apoptosis was attenuated by propofol in a dose-dependent manner. Furthermore, ELISA assays demonstrated that the ratio of angiotensin (1-7) (Ang (1-7)) to Ang II was increased after propofol treatment. We examined the expression of ACE2, Ang (1-7) and Mas and found that the ACE2-Ang (1-7)-Mas axis was up-regulated by propofol, while ACE2 overexpression increased phosphorylated endothelial nitric oxide synthase (phosphorylated eNOS) expression and siACE2 resulted in the repression of endothelial nitric oxide synthase (eNOS) phosphorylation. In conclusion, our study revealed that propofol can inhibit endothelial cell apoptosis induced by Ang II by activating the ACE2-Ang (1-7)-Mas axis and further up-regulating the expression and phosphorylation of eNOS.
血管紧张素 II(AngII)是一种血管活性肽,可升高动脉血压并导致高血压,据报道可直接诱导血管内皮细胞凋亡。最近的研究表明,异丙酚预处理可减轻人冠状动脉内皮细胞中血管紧张素 II 诱导的细胞凋亡。然而,其潜在机制在很大程度上仍不清楚。在这里,我们研究了人脐静脉内皮细胞(HUVEC)在存在或不存在异丙酚处理的情况下,受到血管紧张素 II 诱导的凋亡,并发现血管紧张素 II 诱导的凋亡被异丙酚以剂量依赖的方式减弱。此外,ELISA 检测表明,在异丙酚处理后,血管紧张素(1-7)(Ang(1-7))与 Ang II 的比值增加。我们检测了 ACE2、Ang(1-7)和 Mas 的表达,发现 ACE2-Ang(1-7)-Mas 轴被异丙酚上调,而 ACE2 过表达增加了磷酸化内皮型一氧化氮合酶(磷酸化 eNOS)的表达,siACE2 则抑制了内皮型一氧化氮合酶(eNOS)的磷酸化。总之,我们的研究表明,异丙酚通过激活 ACE2-Ang(1-7)-Mas 轴,进一步上调 eNOS 的表达和磷酸化,从而抑制 Ang II 诱导的内皮细胞凋亡。