Angiotensin II prevents calcification in vascular smooth muscle cells by enhancing magnesium influx
Angiotensin II prevents calcification in vascular smooth muscle cells by enhancing magnesium influx
复制标题
DOI：
10.1111/eci.12517
复制
发表时间：
2015-11-01
影响因子：
5.5
通讯作者：
Almaden, Yolanda
中科院分区：
文献类型：
--
作者：
Herencia, Carmen;Encarnacion Rodriguez-Ortiz, M.;Almaden, Yolanda
背景血管钙化（VC）在慢性肾脏病（CKD）患者中非常常见。低镁水平与VC相关，最近的体外研究证实了镁的保护作用，这是通过其通过瞬时受体电位Melastatin 7（TRPM 7）通道进入VSMC介导的。血管紧张素II（Angiotensin II，Ang II）在VC中的作用尚不清楚。由于Ang II能够刺激TRPM 7活性，我们推测它可能会阻止VC。因此，本研究的目的是解剖血管紧张素II对VC的直接影响。Materials and MethodsWe worked with a model of high phosphate（HP）-induced calcification in human aortic smooth muscle cells，which similarly the CKD-related VC.ResultsAddition of Ang II to cells growing in HP reduced calcification，which is associated with the upregulation of the osteogenic factors BMP 2，Runx 2/Cbfa 1，Osterix and ALP.结果发现，镁离子进入HP钙化细胞的数量减少，Ang II处理可避免这种减少，而TRPM 7抑制剂2-APB可逆转这种减少。Ang Ⅱ的保护作用与AT 1 R激活ERK 1/2 MAPK有关。HP诱导的钙化也与经典的Wnt/β-catenin通路的上调，而其下调与钙化的衰减由AngII.ConclusionAs假设，血管紧张素II防止磷酸盐诱导的钙化VSMCs，这似乎介导的镁流入的增加和ERK 1/2的激活和经典的Wnt/β-catenin信号通路的抑制。
BackgroundVascular calcification (VC) is highly prevalent in patients with chronic kidney disease (CKD). Low magnesium levels are associated with VC, and recent invitro studies confirm a protective role of magnesium, which is mediated by its entry into the VSMCs through the Transient Receptor Potential Melastatin 7 (TRPM7) channel. The role of Angiotensin II (Ang II) on VC is still unclear. As Ang II is able to stimulate TRPM7 activity, we hypothesize that it might prevent VC. Thus, the aim of this study was to dissect the direct effect of Ang II on VC.Materials and methodsWe worked with a model of high phosphate (HP)-induced calcification in human aortic smooth muscle cells, which resembles the CKD-related VC.ResultsAddition of Ang II to cells growing in HP decreased calcification, which was associated with the upregulation of the osteogenic factors BMP2, Runx2/Cbfa1, Osterix and ALP. A reduction of magnesium entry into the HP-calcifying cells was found. The treatment with Ang II avoided this reduction, which was reversed by the cotreatment with the TRPM7-inhibitor 2-APB. The protective effect of Ang II was related to AT1R-induced ERK1/2 MAPKinase activation. HP-induced calcification was also associated with the upregulation of the canonical Wnt/beta-catenin pathway, while its downregulation was related to attenuation of calcification by AngII.ConclusionAs hypothesized, Ang II prevented phosphate-induced calcification in VSMCs, which appears mediated by the increase of magnesium influx and by the activation of the ERK1/2 and the inhibition of the canonical Wnt/beta-catenin signalling pathways.