Fang Zhou, Li Xiang, Liu Junying, Lee Haekyung, Salciccioli Louis, Lazar Jason, Zhang Ming
Department of Anesthesiology, USA.
Department of Medicine, SUNY Downstate Health Science University, 450 Clarkson Avenue, Brooklyn, NY, 11203, USA.
Biochem Biophys Rep. 2023 Jan 26;33:101434. doi: 10.1016/j.bbrep.2023.101434. eCollection 2023 Mar.
Coronary heart disease leading to myocardial ischemia is a major cause of heart failure. A hallmark of heart failure is myocardial fibrosis. Using a murine model of myocardial ischemia/reperfusion injury (IRI), we showed that, following IRI, in mice genetically deficient in the central factor of complement system, C3, myocardial necrosis was reduced compared with WT mice. Four weeks after the ischemic period, the C3 mice had significantly less cardiac fibrosis and better cardiac function than the WT controls. Overall, our results suggest that innate immune response through complement C3 plays an important role in necrotic cell death, which contributes to the cardiac fibrosis that underlies post-infarction heart failure.
导致心肌缺血的冠心病是心力衰竭的主要原因。心力衰竭的一个标志是心肌纤维化。利用心肌缺血/再灌注损伤（IRI）的小鼠模型，我们发现，在IRI后，与野生型（WT）小鼠相比，在补体系统中心因子C3基因缺陷的小鼠中，心肌坏死减少。缺血期四周后，C3基因缺陷小鼠的心脏纤维化明显少于野生型对照小鼠，心脏功能也更好。总体而言，我们的结果表明，通过补体C3的天然免疫反应在坏死性细胞死亡中起重要作用，而坏死性细胞死亡会导致心肌梗死后心力衰竭所依据的心脏纤维化。
