Pei Huawei, Zhang Haiyue, Tian Chuan, Sun Xiaogang, Qian Xiangyang, Meng Yanhai, Guo Xiaobo, Chang Qian
Department of Cardiovascular Surgery, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China.
Department of Neurology, Xuanwu Hospital Capital Medical University, Beijing, China.
Cardiology. 2021;146(5):646-655. doi: 10.1159/000513143. Epub 2021 Jun 29.
Extracellular matrix disorder and cellular phenotype transformation are the major histopathological features associated with ascending aortic aneurysms. Rare studies have investigated the relationship between cellular phenotype transformation and the abnormalities of the matrix constituents. In this study, we investigated whether the cellular phenotype transformation resulted in the extracellular matrix disorder.
Aortic samples were obtained from 20 patients undergoing operations for ascending aortic aneurysms. Control aortic samples were obtained from 15 patients who underwent coronary artery bypass graft. The protein levels of osteopontin (OPN), collagen, and elastin were examined using Western blot, and quantitative reverse transcriptase-PCR was used to analyze the mRNA expression of collagen and elastin. In vitro experiment, vascular smooth muscle cells (VSMCs) were treated with recombinant human OPN (rh-OPN) or p38 MAPK inhibitor (SB203580) to investigate whether OPN and p38 MAPK regulated the expression of collagen and elastin.
The protein level of OPN and collagen III increased in ascending aortic aneurysm samples, compared with controls (p < 0.05). There was no difference in the protein level of elastin between aneurysm tissues and the controls. VSMCs treated with rh-OPN increased the collagen III and elastin protein level and mRNA expression (p < 0.05). Cells treated with SB203580 decreased the collagen III and elastin protein level and mRNA expression (p < 0.05). Furthermore, VSMCs incubated with SB203580 reduced the rh-OPN-induced production of collagen III and elastin (p < 0.05).
OPN, the proliferative VSMCs maker, increased the expression of extracellular matrix. OPN/p38 MAPK signaling pathways may protect against ascending aortic aneurysm progression.
细胞外基质紊乱和细胞表型转化是升主动脉瘤相关的主要组织病理学特征。很少有研究探讨细胞表型转化与基质成分异常之间的关系。在本研究中，我们调查了细胞表型转化是否导致细胞外基质紊乱。
从20例行升主动脉瘤手术的患者中获取主动脉样本。对照主动脉样本来自15例行冠状动脉旁路移植术的患者。使用蛋白质印迹法检测骨桥蛋白（OPN）、胶原蛋白和弹性蛋白的蛋白质水平，并使用定量逆转录聚合酶链反应分析胶原蛋白和弹性蛋白的mRNA表达。在体外实验中，用重组人OPN（rh-OPN）或p38丝裂原活化蛋白激酶抑制剂（SB203580）处理血管平滑肌细胞（VSMC），以研究OPN和p38丝裂原活化蛋白激酶是否调节胶原蛋白和弹性蛋白的表达。
与对照组相比，升主动脉瘤样本中OPN和III型胶原蛋白的蛋白质水平升高（p<0.05）。动脉瘤组织和对照组之间弹性蛋白的蛋白质水平没有差异。用rh-OPN处理的VSMC增加了III型胶原蛋白和弹性蛋白的蛋白质水平及mRNA表达（p<0.05）。用SB203580处理的细胞降低了III型胶原蛋白和弹性蛋白的蛋白质水平及mRNA表达（p<0.05）。此外，用SB203580孵育的VSMC减少了rh-OPN诱导的III型胶原蛋白和弹性蛋白的产生（p<0.05）。
OPN作为增殖性VSMC的标志物，增加了细胞外基质的表达。OPN/p38丝裂原活化蛋白激酶信号通路可能预防升主动脉瘤进展。
