Wu Z, Wang Z, Xu P, Zhang M, Cheng L, Gong B
Department of Cardiovascular Surgery, Renmin Hospital of Wuhan University, Wuhan 430060, China.
Curr Mol Med. 2017;17(8):568-579. doi: 10.2174/1566524018666180222123518.
Little is known about the pathogenesis of acute lung injury (ALI) complicated with acute aortic dissection (AAD).
We aim to investigate the roles of macrophages-derived matrix metalloproteinase 9 (MMP9) in the development of ALI complicated with AAD and factors involved in the recruitment of macrophages.
This study included three parts: (i) Determination of serum MMPs, angiotensin II (AngII) and MCP-1 in patients with AAD complicated with ALI or AAD only, non-ruptured chronic aortic aneurysm patients or healthy volunteers using ELISA method. (ii) A novel AAD complicated with ALI model was established by infusing angiotensin II (AngII) to immature rats treated with β-aminopropionitrile monofumarate (BAPN) to identify the potential roles of MMP9 and MCP-1 in AAD complicated with ALI. (iii) Cultured pulmonary microvascular endothelial cell (PMVEC) line was used to investigate how AngII was involved in the release of MCP-1 in rat pulmonary vascular endothelial cells.
Serum MMP9, AngII and MCP-1 were remarkably elevated in patients with AAD complicated with ALI. The MMP9 expressed in pulmonary tissues was derived from macrophages. In the animal model, the release of MMP9 from macrophages finally resulted in ALI, while inhibition of MMP9 and MCP-1 contributed to decreased incidence of AAD complicated with ALI. In vitro experiments indicated that AngII triggered overexpression of MCP-1 in PMVECs by activating NF-κB signaling pathway.
AAD complicated with ALI is highly associated with the macrophages infiltrating the pulmonary interstitial tissue and released MMP9 in response to angiotensin II. MCP-1 is closely related to the recruitment of macrophages.
关于急性肺损伤（ALI）合并急性主动脉夹层（AAD）的发病机制知之甚少。
我们旨在研究巨噬细胞衍生的基质金属蛋白酶9（MMP9）在ALI合并AAD发生发展中的作用以及参与巨噬细胞募集的因素。
本研究包括三个部分：（i）采用酶联免疫吸附测定（ELISA）法测定AAD合并ALI患者、单纯AAD患者、未破裂慢性主动脉瘤患者或健康志愿者血清中的基质金属蛋白酶（MMPs）、血管紧张素II（AngII）和单核细胞趋化蛋白-1（MCP-1）。（ii）通过向用单氟马来酸β-氨基丙腈（BAPN）处理的未成熟大鼠输注血管紧张素II（AngII），建立一种新的AAD合并ALI模型，以确定MMP9和MCP-1在AAD合并ALI中的潜在作用。（iii）使用培养的肺微血管内皮细胞（PMVEC）系研究AngII如何参与大鼠肺血管内皮细胞中MCP-1的释放。
AAD合并ALI患者血清中的MMP9、AngII和MCP-1显著升高。肺组织中表达的MMP9来源于巨噬细胞。在动物模型中，巨噬细胞释放的MMP9最终导致ALI，而抑制MMP9和MCP-1有助于降低AAD合并ALI的发生率。体外实验表明，AngII通过激活核因子κB（NF-κB）信号通路触发PMVECs中MCP-1的过表达。
AAD合并ALI与肺间质组织中浸润的巨噬细胞以及对血管紧张素II作出反应而释放的MMP9高度相关。MCP-1与巨噬细胞的募集密切相关。
