Complement C1q-induced activation of β-catenin signalling causes hypertensive arterial remodelling

Tomokazu Sumida, Atsuhiko T. Naito, Seitaro Nomura, Akito Nakagawa, Tomoaki Higo, Akihito Hashimoto, Katsuki Okada, Taku Sakai, Masamichi Ito, Toshihiro Yamaguchi, Toru Oka, Hiroshi Akazawa, Jong-Kook Lee, Tohru Minamino, Stefan Offermanns, Tetsuo Noda, Marina Botto, Yoshio Kobayashi, Hiroyuki Morita, Ichiro Manabe, Toshio Nagai, Ichiro Shiojima and Issei Komuro ()
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Tomokazu Sumida: The University of Tokyo Graduate School of Medicine
Atsuhiko T. Naito: The University of Tokyo Graduate School of Medicine
Seitaro Nomura: The University of Tokyo Graduate School of Medicine
Akito Nakagawa: Osaka University Graduate School of Medicine
Tomoaki Higo: Osaka University Graduate School of Medicine
Akihito Hashimoto: Osaka University Graduate School of Medicine
Katsuki Okada: Osaka University Graduate School of Medicine
Taku Sakai: Osaka University Graduate School of Medicine
Masamichi Ito: The University of Tokyo Graduate School of Medicine
Toshihiro Yamaguchi: The University of Tokyo Graduate School of Medicine
Toru Oka: CREST, Japan Science and Technology Agency
Hiroshi Akazawa: The University of Tokyo Graduate School of Medicine
Jong-Kook Lee: CREST, Japan Science and Technology Agency
Tohru Minamino: Niigata University Graduate School of Medical and Dental Sciences
Stefan Offermanns: Max-Planck-Institute for Heart and Lung Research
Tetsuo Noda: The Cancer Institute, Japanese Foundation for Cancer Research
Marina Botto: Centre for Complement and Inflammation Research, Imperial College London
Yoshio Kobayashi: Chiba University Graduate School of Medicine
Hiroyuki Morita: The University of Tokyo Graduate School of Medicine
Ichiro Manabe: The University of Tokyo Graduate School of Medicine
Toshio Nagai: Chiba University Graduate School of Medicine
Ichiro Shiojima: CREST, Japan Science and Technology Agency
Issei Komuro: The University of Tokyo Graduate School of Medicine

Nature Communications, 2015, vol. 6, issue 1, 1-12

Abstract: Abstract 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.

Date: 2015
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DOI: 10.1038/ncomms7241

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