FNDC4 alleviates cardiac ischemia/reperfusion injury through facilitating HIF1α-dependent cardiomyocyte survival and angiogenesis in male mice.

ABSTRACT: Fibronectin type III domain-containing (FNDC) proteins play critical roles in cellular homeostasis and cardiac injury, and our recent findings define FNDC5 as a promising cardioprotectant against doxorubicin- and aging-related cardiac injury. FNDC4 displays a high homology with FNDC5; however, its role and mechanism in cardiac ischemia/reperfusion (I/R) injury remain elusive. Here, we show that cardiac and plasma FNDC4 levels are elevated during I/R injury in a hypoxia-inducible factor 1α (HIF1α)-dependent manner. Cardiac-specific FNDC4 overexpression facilitates, while cardiac-specific FNDC4 knockdown inhibits cardiomyocyte survival and angiogenesis in I/R-stressed hearts of male mice through regulating the proteasomal degradation of HIF1α. Interestingly, FNDC4 does not directly stimulate

SUBMITTER: Zhang X 

PROVIDER: S-EPMC11549404 | biostudies-literature | 2024 Nov

REPOSITORIES: biostudies-literature