期刊
NATURE COMMUNICATIONS
卷 13, 期 1, 页码 -出版社
NATURE PORTFOLIO
DOI: 10.1038/s41467-022-33152-9
关键词
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资金
- JSPS KAKENHI [16H05304, 16K15415, 18K08047, 19H03622, 20H03678, 20K08461, 20K08193]
- SENSHIN Medical Research Foundation
- Fukuda Foundation for Medical Technology
- Daiwa Securities Health Foundation
- Miyata Cardiac Research Promotion Foundation
- Kawano Masanori Memorial Public Interest Incorporated Foundation for Promotion of Pediatrics
Right ventricular (RV) failure is clinically crucial, but there is no specific therapy yet. The study demonstrates the crucial role of the C3-Cfd-C3aR axis in right ventricular failure, suggesting potential therapeutic targets for this condition.
Right ventricular (RV) failure is clinically crucial, but there is no specific therapy. Here, the authors show that the complement alternative pathway is activated in RV failure and that blockade of the pathway ameliorates RV failure in mice. Failure of the right ventricle plays a critical role in any type of heart failure. However, the mechanism remains unclear, and there is no specific therapy. Here, we show that the right ventricle predominantly expresses alternative complement pathway-related genes, including Cfd and C3aR1. Complement 3 (C3)-knockout attenuates right ventricular dysfunction and fibrosis in a mouse model of right ventricular failure. C3a is produced from C3 by the C3 convertase complex, which includes the essential component complement factor D (Cfd). Cfd-knockout mice also show attenuation of right ventricular failure. Moreover, the plasma concentration of CFD correlates with the severity of right ventricular failure in patients with chronic right ventricular failure. A C3a receptor (C3aR) antagonist dramatically improves right ventricular dysfunction in mice. In summary, we demonstrate the crucial role of the C3-Cfd-C3aR axis in right ventricular failure and highlight potential therapeutic targets for right ventricular failure.
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