Exercise protects aged mice against coronary endothelial senescence via FUNDC1-dependent mitophagy

• DOI: 10.1016/j.redox.2023.102693
• Publication Date: 2023-04-01T23:30:58Z
• Authors: Lijie Ma; Kaifeng Li; Wenxiang Wei; Jiaheng Zhou; Ze Li; Tuo Zhang; Yunshu Wangsun; Fei Tian; Qianqian Dong; Haifeng Zhang; Wenjuan Xing
• Keywords: Senescence; Endothelial Dysfunction

Vascular aging contributes to adverse changes in organ function and is a significant indicator of major cardiac events. Endothelial cells (ECs) participate aging-provoked coronary vascular pathology. Regular exercise associated with preservation arterial humans. However, the molecular basis not well understood. The present study was aimed determine effects on endothelial senescence whether mitochondrial clearance regulator FUN14 domain containing 1 (FUNDC1)-related mitophagy homeostasis were involved. In mouse arteries, FUNDC1 levels showed gradually decrease age. Both microvascular (CMECs) significantly reduced aged mice rescued by training. Exercise also alleviated CMECs as evidenced β-galactosidase activity markers, prevented abnormal cell migration, proliferation, eNOS activation from mice, improved endothelium-dependent vasodilation artery, myocardial neutrophil infiltration inflammatory cytokines evoked MI/R, restored angiogenesis consequently MI/R injury aging. Importantly, deletion abolished protective roles overexpression ECs adeno-associated virus (AAV) reversed injury. Mechanistically, PPARγ played an important role regulating expressions endothelium under exercise-induced laminar shear stress. conclusion, prevents arteries via increasing PPARγ-dependent manner, subsequently protects against These findings highlight FUNDC1-mediated potential therapeutic target that vulnerability.