Role of matrix Gla protein in angiotensin II-induced exacerbation of vascular calcification
Role of matrix Gla protein in angiotensin II-induced exacerbation of vascular calcification
复制标题
DOI：
10.1152/ajpheart.00826.2011
复制
发表时间：
2012-09-01
影响因子：
4.8
通讯作者：
Agrawal, Devendra K.
中科院分区：
文献类型：
--
作者：
Jia, Guanghong;Stormont, Ryan M.;Agrawal, Devendra K.
贾刚，Stormont RM, Gangahar DM, Agrawal DK。基质Gla蛋白在血管紧张素ii诱导的血管钙化加剧中的作用。[J] .中国生物医学工程学报，2016,31(3):532 - 532。首次发表于2012年7月13日；doi: 10.1152 / ajpheart.00826.2011。血管钙化预测动脉粥样硬化、糖尿病和终末期肾脏疾病的心血管事件风险增加。基质玻璃蛋白（MGP），钙化抑制剂，限制磷酸钙沉积在血管壁。导致动脉粥样硬化进展的因素有很多，包括高血压、高脂血症、肾血管紧张素系统和炎症。血管紧张素II （angii）在动脉粥样硬化过程中起着至关重要的作用，不仅通过其升压反应，还通过其促生长和炎症作用。在这项研究中，我们研究了MGP在ANG ii诱导的人血管平滑肌细胞（VSMCs）血管钙化加剧中的作用。分别采用Western blot、real-time PCR、原位末端脱氧核苷酸转移酶介导dUTP缺口末端标记和酶联免疫吸附法检测人VSMCs中MGP、钙化和凋亡的表达。人动脉粥样硬化斑块VSMC钙化增加以负反馈方式上调MGP表达和凋亡。ANG II通过ANG II型1受体和NF-kappa B信号通路通过剂量和时间依赖性途径和体外抑制VSMCs中MGP的表达。同时，MGP抑制体外钙化培养基（2.5 mM P-i）和ANG II诱导的VSMCs的钙化、caspase-3活性、runt相关转录因子2的激活和炎性细胞因子的释放。这些观察结果提供了证据，表明ANG II通过激活转录因子、侏儒相关转录因子2和NF-kappa B，以及调节MGP、炎症细胞因子在人VSMCs中的表达，加剧了血管钙化。
Jia G, Stormont RM, Gangahar DM, Agrawal DK. Role of matrix Gla protein in angiotensin II-induced exacerbation of vascular calcification. Am J Physiol Heart Circ Physiol 303: H523-H532, 2012. First published July 13, 2012; doi:10.1152/ajpheart.00826.2011.-Vascular calcification predicts an increased risk for cardiovascular events in atherosclerosis, diabetes, and end-stage kidney diseases. Matrix Gla protein (MGP), an inhibitor of calcification, limits calcium phosphate deposition in the vessel wall. There are many factors contributing to the progression of atherosclerosis, including hypertension, hyperlipidemia, the reninangiotensin system, and inflammation. Angiotensin II (ANG II) plays a crucial role in the atherogenic process through not only its pressor responses but also its growth-promoting and inflammatory effects. In this study, we investigated the role of MGP in ANG II-induced exacerbation of vascular calcification in human vascular smooth muscle cells (VSMCs). The expression of MGP, calcification, and apoptosis in human VSMCs were examined by Western blot analysis, real-time PCR, in situ terminal deoxynucleotidyltransferase-mediated dUTP nick end labeling, and enzyme-linked immunosorbent assay, respectively. Increase in VSMC calcification in human atherosclerotic plaques upregulates MGP expression and apoptosis in a negative feedback manner. ANG II inhibited MGP expression in VSMCs via and in vitro in a dose- and time-dependent manner through ANG II type 1 receptor and NF-kappa B signaling pathway. Meanwhile, MGP inhibited the calcification, caspase-3 activity, activation of runt-related transcription factor 2, and release of inflammatory cytokines by VSMCs induced by calcification medium (2.5 mM P-i) and ANG II in vitro. These observations provide evidence that ANG II exacerbates vascular calcification through activation of the transcription factors, runt-related transcription factor 2 and NF-kappa B, and regulation of MGP, inflammatory cytokines expression in human VSMCs.