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.
journal_name
Nat Communjournal_title
Nature communicationsauthors
Sumida T,Naito AT,Nomura S,Nakagawa A,Higo T,Hashimoto A,Okada K,Sakai T,Ito M,Yamaguchi T,Oka T,Akazawa H,Lee JK,Minamino T,Offermanns S,Noda T,Botto M,Kobayashi Y,Morita H,Manabe I,Nagai T,Shiojima I,Komurodoi
10.1038/ncomms7241subject
Has Abstractpub_date
2015-02-26 00:00:00pages
6241issn
2041-1723pii
ncomms7241journal_volume
6pub_type
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