Macrophage-Specific NLRC5 Protects From Cardiac Remodeling Through Interaction With HSPA8
Qing Yu, Peinan Ju, Wenxin Kou, Ming Zhai, Yanxi Zeng, Nuerbiyemu Maimaitiaili, Yefei Shi, Xu Xu, Yifan Zhao, Weixia Jian, Mark W. Feinberg, Yawei Xu, Jianhui Zhuang, Wenhui Peng
Abstract
Macrophages regulate inflammation and the process of tissue repair. Therefore, a better understanding of macrophages in the pathogenesis of heart failure is needed. In patients with hypertrophic cardiomyopathy, NLRC5 was significantly increased in circulating monocytes and cardiac macrophages. Myeloid-specific deletion of NLRC5 aggravated pressure overload-induced pathological cardiac remodeling and inflammation. Mechanistically, NLRC5 interacted with HSPA8 and suppressed NF-κB pathway in macrophages. The absence of NLRC5 in macrophages promoted the secretion of cytokines such as interleukin-6 (IL-6), which affected cardiomyocyte hypertrophy and cardiac fibroblast activation. Tocilizumab, an anti-IL-6 receptor antagonist, may be a novel therapeutic strategy for cardiac remodeling and chronic heart failure.