Maffia, P. , Mauro, C., Case, A. and Kemper, C. (2024) Canonical and non-canonical roles of complement in atherosclerosis. Nature Reviews Cardiology, (doi: 10.1038/s41569-024-01016-y) (PMID:38600367) (Early Online Publication)
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Abstract
Cardiovascular diseases are the leading cause of death globally, and atherosclerosis is the major contributor to the development and progression of cardiovascular diseases. Immune responses have a central role in the pathogenesis of atherosclerosis, with the complement system being an acknowledged contributor. Chronic activation of liver-derived and serum-circulating canonical complement sustains endothelial inflammation and innate immune cell activation, and deposition of complement activation fragments on inflamed endothelial cells is a hallmark of atherosclerotic plaques. However, increasing evidence indicates that liver-independent, cell-autonomous and non-canonical complement activities are underappreciated contributors to atherosclerosis. Furthermore, complement activation can also have atheroprotective properties. These specific detrimental or beneficial contributions of the complement system to the pathogenesis of atherosclerosis are dictated by the location of complement activation and engagement of its canonical versus non-canonical functions in a temporal fashion during atherosclerosis progression. In this Review, we summarize the classical and the emerging non-classical roles of the complement system in the pathogenesis of atherosclerosis and discuss potential strategies for therapeutic modulation of complement for the prevention and treatment of atherosclerotic cardiovascular disease.
| Item Type: | Articles |
|---|---|
| Additional Information: | Work in the Kemper laboratory is supported in part by the Intramural Research Program of the National Institutes of Health, National Heart, Lung, and Blood Institute (ZIA/hl006223 to C.K.), the NIH-OXCAM Scholars Program and a Gates Cambridge Scholarship (A.C.). Work in the Maffia laboratory is supported in part by British Heart Foundation grants (PG/19/84/34771, FS/19/56/34893 A, PG/21/10541, PG/21/10557, PG/21/10634) and the Italian Ministry of University and Research (MUR) PRIN 2022 (2022T45AXH). C.M. is supported by a British Heart Foundation Senior Research Fellowship (FS/SBSRF/22/31031). |
| Status: | Early Online Publication |
| Refereed: | Yes |
| Glasgow Author(s) Enlighten ID: | Maffia, Professor Pasquale |
| Authors: | Maffia, P., Mauro, C., Case, A., and Kemper, C. |
| College/School: | College of Medical Veterinary and Life Sciences > School of Infection & Immunity |
| Journal Name: | Nature Reviews Cardiology |
| Publisher: | Nature Research |
| ISSN: | 1759-5002 |
| ISSN (Online): | 1759-5010 |
| Published Online: | 10 April 2024 |
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