Wu Zhiyong, Dai Feifeng, Ren Wei, Liu Huagang, Li Bowen, Chang Jinxing
Department of Cardiovascular Surgery, Wuhan University Renmin Hospital Wuhan, China.
Am J Transl Res. 2016 Jan 15;8(1):28-36. eCollection 2016.
Patients with acute aortic dissection (AAD) usually showed acute lung injury (ALI). However, its pathogenesis is still not well defined. Apoptosis of pulmonary microvascular endothelial cells (PMVECs) is closely related to the alveolus-capillary barrier injury and the increased vascular permeability. In this study, we aim to investigate the human PMVECs (hPMVECs) apoptosis induced by angiotensin II (AngII) and monocyte chemoattractant protein-1 (MCP-1) and their potential interaction in the pathogenesis of AAD complicated with ALI. Fifty-eight newly diagnosed AAD, 12 matched healthy individuals were included. Pulmonary tissues of AAD complicated with lung injury were obtained from 2 cadavers to determine the levels of AngII type 1 receptor (AT1-R) and MCP-1. Serum AngII was measured using commercial ELISA kit. H&E staining and immunohistostaining were performed to determine the expression of AT1-R and MCP-1. For the in vitro experiment, hPMVECs were divided into control, AngII group, AngII+Bindarit group and Bindarit group, respectively. Flow cytometry was performed to analyze the apoptosis in each group. Reverse transcription-polymerase chain reaction was performed to determine the mRNA expression of MCP-1. Western blot analysis was performed to evaluate the expression of MCP-1 and apoptosis related protein. Apoptosis of hPMVECs was observed in the lung tissues in the cadavers with AAD complicated with ALI. Besides, the expression of AT1-R and MCP-1 was remarkably elevated. Compared with normal individuals and the non-lung injury AAD patients, the expression of serum AngII was remarkably elevated in AAD patients complicated with ALI. In vitro experiments showed AngII contributed to the apoptosis and elevation of MCP1 in hPMVECs. Besides, it involved in the down-regulation of Bcl-2 protein, and up-regulation of Bax and Caspase-3. Such phenomenon was completely reversed after administration of MCP-1 inhibitor (Bindarit). The production of MCP-1 and cellular apoptosis induced by AngII in hPMVECs are closely related to the pathogenesis of AAD complicated with ALI. The association between MCP-1 and AngII is crucial in the apoptosis of hPMVECs.
急性主动脉夹层（AAD）患者通常会出现急性肺损伤（ALI）。然而，其发病机制仍未完全明确。肺微血管内皮细胞（PMVECs）凋亡与肺泡 - 毛细血管屏障损伤及血管通透性增加密切相关。在本研究中，我们旨在探讨血管紧张素II（AngII）和单核细胞趋化蛋白 -1（MCP -1）诱导的人肺微血管内皮细胞（hPMVECs）凋亡及其在AAD合并ALI发病机制中的潜在相互作用。纳入了58例新诊断的AAD患者和12例匹配的健康个体。从2具尸体获取AAD合并肺损伤的肺组织，以测定血管紧张素II 1型受体（AT1 -R）和MCP -1的水平。使用商用ELISA试剂盒检测血清AngII。进行苏木精 - 伊红（H&E）染色和免疫组织化学染色以确定AT1 -R和MCP -1的表达。在体外实验中，将hPMVECs分别分为对照组、AngII组、AngII + Bindarit组和Bindarit组。采用流式细胞术分析各组细胞凋亡情况。进行逆转录 - 聚合酶链反应以测定MCP -1的mRNA表达。采用蛋白质免疫印迹分析评估MCP -1和凋亡相关蛋白的表达。在合并ALI的AAD尸体的肺组织中观察到hPMVECs凋亡。此外，AT1 -R和MCP -1的表达显著升高。与正常个体和无肺损伤的AAD患者相比，合并ALI的AAD患者血清AngII表达显著升高。体外实验表明，AngII促进hPMVECs凋亡并使MCP1升高。此外，它参与Bcl -2蛋白的下调以及Bax和Caspase -3的上调。给予MCP -1抑制剂（Bindarit）后，这种现象完全逆转。AngII诱导的hPMVECs中MCP -1产生和细胞凋亡与AAD合并ALI的发病机制密切相关。MCP -1与AngII之间的关联在hPMVECs凋亡中至关重要。
