Macrophage-Specific NLRC5 Protects From Cardiac Remodeling Through Interaction With HSPA8

JACC Basic Transl Sci. 2023 Jan 18;8(5):479-496. doi: 10.1016/j.jacbts.2022.10.001. eCollection 2023 May.

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.

Keywords: NOD-like receptor; cardiac remodeling; heart failure; immunomodulatory therapy; macrophages.