title: Complement C1q-induced activation of β-catenin signalling causes hypertensive arterial remodelling.
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.
authors.affiliation: 1] Department of Cardiovascular Medicine, The University of Tokyo Graduate School of Medicine, Tokyo 113-8655, Japan [2] CREST, Japan Science and Technology Agency, Tokyo 102-0075, Japan.
authors.forename: Tomokazu
authors.initials: T
authors.lastname: Sumida
authors.affiliation: 1] Department of Cardiovascular Medicine, The University of Tokyo Graduate School of Medicine, Tokyo 113-8655, Japan [2] CREST, Japan Science and Technology Agency, Tokyo 102-0075, Japan [3] Department of Cardiovascular Medicine, Osaka University Graduate School of Medicine, Osaka 565-0871, Japan.
authors.forename: Atsuhiko T
authors.initials: AT
authors.lastname: Naito
authors.affiliation: Department of Cardiovascular Medicine, The University of Tokyo Graduate School of Medicine, Tokyo 113-8655, Japan.
authors.forename: Seitaro
authors.initials: S
authors.lastname: Nomura
authors.affiliation: Department of Cardiovascular Medicine, Osaka University Graduate School of Medicine, Osaka 565-0871, Japan.
authors.forename: Akito
authors.initials: A
authors.lastname: Nakagawa
authors.affiliation: Department of Cardiovascular Medicine, Osaka University Graduate School of Medicine, Osaka 565-0871, Japan.
authors.forename: Tomoaki
authors.initials: T
authors.lastname: Higo
authors.affiliation: Department of Cardiovascular Medicine, Osaka University Graduate School of Medicine, Osaka 565-0871, Japan.
authors.forename: Akihito
authors.initials: A
authors.lastname: Hashimoto
authors.affiliation: Department of Cardiovascular Medicine, Osaka University Graduate School of Medicine, Osaka 565-0871, Japan.
authors.forename: Katsuki
authors.initials: K
authors.lastname: Okada
authors.affiliation: Department of Cardiovascular Medicine, Osaka University Graduate School of Medicine, Osaka 565-0871, Japan.
authors.forename: Taku
authors.initials: T
authors.lastname: Sakai
authors.affiliation: Department of Cardiovascular Medicine, The University of Tokyo Graduate School of Medicine, Tokyo 113-8655, Japan.
authors.forename: Masamichi
authors.initials: M
authors.lastname: Ito
authors.affiliation: Department of Cardiovascular Medicine, The University of Tokyo Graduate School of Medicine, Tokyo 113-8655, Japan.
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Yamaguchi
authors.affiliation: 1] CREST, Japan Science and Technology Agency, Tokyo 102-0075, Japan [2] Department of Cardiovascular Medicine, Osaka University Graduate School of Medicine, Osaka 565-0871, Japan.
authors.forename: Toru
authors.initials: T
authors.lastname: Oka
authors.affiliation: 1] Department of Cardiovascular Medicine, The University of Tokyo Graduate School of Medicine, Tokyo 113-8655, Japan [2] CREST, Japan Science and Technology Agency, Tokyo 102-0075, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Akazawa
authors.affiliation: 1] CREST, Japan Science and Technology Agency, Tokyo 102-0075, Japan [2] Department of Cardiovascular Medicine, Osaka University Graduate School of Medicine, Osaka 565-0871, Japan.
authors.forename: Jong-Kook
authors.initials: JK
authors.lastname: Lee
authors.affiliation: Department of Cardiovascular Biology and Medicine, Niigata University Graduate School of Medical and Dental Sciences, Niigata 951-8510, Japan.
authors.forename: Tohru
authors.initials: T
authors.lastname: Minamino
authors.affiliation: Department of Pharmacology, Max-Planck-Institute for Heart and Lung Research, Bad Nauheim D-61231, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Offermanns
authors.affiliation: Department of Cell Biology, The Cancer Institute, Japanese Foundation for Cancer Research, Tokyo 135-8550, Japan.
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Noda
authors.affiliation: Centre for Complement and Inflammation Research, Department of Medicine, Imperial College London, London SW7 2AZ, UK.
authors.forename: Marina
authors.initials: M
authors.lastname: Botto
authors.affiliation: Department of Cardiovascular Medicine, Chiba University Graduate School of Medicine, Chiba 260-8670, Japan.
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Kobayashi
authors.affiliation: Department of Cardiovascular Medicine, The University of Tokyo Graduate School of Medicine, Tokyo 113-8655, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Morita
authors.affiliation: Department of Cardiovascular Medicine, The University of Tokyo Graduate School of Medicine, Tokyo 113-8655, Japan.
authors.forename: Ichiro
authors.initials: I
authors.lastname: Manabe
authors.affiliation: Department of Cardiovascular Medicine, Chiba University Graduate School of Medicine, Chiba 260-8670, Japan.
authors.forename: Toshio
authors.initials: T
authors.lastname: Nagai
authors.affiliation: 1] CREST, Japan Science and Technology Agency, Tokyo 102-0075, Japan [2] Department of Medicine II, Kansai Medical University, Osaka 573-1191, Japan.
authors.forename: Ichiro
authors.initials: I
authors.lastname: Shiojima
authors.affiliation: 1] Department of Cardiovascular Medicine, The University of Tokyo Graduate School of Medicine, Tokyo 113-8655, Japan [2] CREST, Japan Science and Technology Agency, Tokyo 102-0075, Japan [3] Department of Cardiovascular Medicine, Osaka University Graduate School of Medicine, Osaka 565-0871, Japan.
authors.forename: Issei
authors.initials: I
authors.lastname: Komuro
mesh_terms: D000818:Animals; D001012:Aorta, Abdominal / Q000503:physiopathology; D049109:Cell Proliferation; D002478:Cells, Cultured; D015922:Complement C1q / Q000378:metabolism*; D006973:Hypertension / Q000276:immunology / Q000378:metabolism / Q000503:physiopathology*; D008264:Macrophages / Q000502:physiology; D008297:Male; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009131:Muscle, Smooth, Vascular / Q000503:physiopathology; D032389:Myocytes, Smooth Muscle / Q000502:physiology; D066253:Vascular Remodeling; D051176:beta Catenin / Q000378:metabolism*
chemical_list: D051176:beta Catenin; D015922:Complement C1q