Complement C1q-induced activation of β-catenin signalling causes hypertensive arterial remodelling.
Complement C1q-induced activation of β-catenin signalling causes hypertensive arterial remodelling.
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DOI：
10.1038/ncomms7241
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发表时间：
2015-02-26
影响因子：
16.6
通讯作者：
Komuro, Issei
中科院分区：
文献类型：
--
作者：
Sumida, Tomokazu;Naito, Atsuhiko T.;Nomura, Seitaro;Nakagawa, Akito;Higo, Tomoaki;Hashimoto, Akihito;Okada, Katsuki;Sakai, Taku;Ito, Masamichi;Yamaguchi, Toshihiro;Oka, Toru;Akazawa, Hiroshi;Lee, Jong-Kook;Minamino, Tohru;Offermanns, Stefan;Noda, Tetsuo;Botto, Marina;Kobayashi, Yoshio;Morita, Hiroyuki;Manabe, Ichiro;Nagai, Toshio;Shiojima, Ichiro;Komuro, Issei
高血压引起动脉结构重塑，导致动脉硬化和终末器官损伤。血管平滑肌细胞（VSMCs）增生和免疫细胞浸润是高血压动脉重塑的标志。然而，动脉重塑的精确分子机制仍然难以捉摸。我们最近报道了补体C1 q激活β-catenin信号传导，而不依赖于Wnt。在这里，我们展示了补体C1诱导的β-连环蛋白信号激活在高血压动脉重塑中的关键作用。在血压升高后观察到β-catenin的激活和VSMCs的增殖，这可以通过β-catenin信号传导的遗传和化学抑制来防止。巨噬细胞耗竭和C1 qa基因缺失可减弱高血压诱导的β-catenin信号传导、VSMCs增殖和病理性动脉重塑。我们的研究结果揭示了补体C1和动脉重塑之间的联系，并表明C1诱导的β-连环蛋白信号转导激活成为预防高血压患者动脉硬化的新治疗靶点。 巨噬细胞在高血压诱导的动脉重塑中的作用知之甚少。Sumida等人的研究表明，高血压驱使交替激活的巨噬细胞分泌补体C1 q蛋白，这反过来又增强了动脉平滑肌细胞中的增殖性β-连环蛋白信号传导。
Hypertension induces structural remodelling of arteries, which leads to arteriosclerosis and end-organ damage. Hyperplasia of vascular smooth muscle cells (VSMCs) and infiltration of immune cells are the hallmark of hypertensive arterial remodelling. However, the precise molecular mechanisms of arterial remodelling remain elusive. We have recently reported that complement C1q activates β-catenin signalling independent of Wnts. Here, we show a critical role of complement C1-induced activation of β-catenin signalling in hypertensive arterial remodelling. Activation of β-catenin and proliferation of VSMCs were observed after blood-pressure elevation, which were prevented by genetic and chemical inhibition of β-catenin signalling. Macrophage depletion and C1qa gene deletion attenuated the hypertension-induced β-catenin signalling, proliferation of VSMCs and pathological arterial remodelling. Our findings unveil the link between complement C1 and arterial remodelling and suggest that C1-induced activation of β-catenin signalling becomes a novel therapeutic target to prevent arteriosclerosis in patients with hypertension. The role of macrophages in hypertension-induced arterial remodeling is poorly understood. Here, Sumida et al. show that high blood pressure drives the alternatively activated macrophages to secrete complement C1q protein, which in turn elicits proliferative β-catenin signalling in the arterial smooth muscle cells.
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影响因子：
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