Myeloid DRP1 deficiency limits revascularization in ischemic muscles via inflammatory macrophage polarization and metabolic reprogramming.

ABSTRACT: Macrophages play a crucial role in promoting perfusion recovery and revascularization after ischemia through antiinflammatory polarization, a process essential for the treatment of peripheral artery disease (PAD). Mitochondrial dynamics, particularly regulated by the fission protein DRP1, are closely linked to macrophage metabolism and inflammation. However, the role of DRP1 in reparative neovascularization remains unexplored. Here, we show that DRP1 expression was increased in F4/80+ macrophages within ischemic muscle on day 3 after hind limb ischemia (HLI), an animal model of PAD. Mice lacking Drp1 in myeloid cells exhibited impaired limb perfusion recovery, angiogenesis, and muscle regeneration after HLI. These effects were associated with increased proinflammatory M1-like macrophages,

SUBMITTER: Yadav S 

PROVIDER: S-EPMC11721294 | biostudies-literature | 2025 Jan

REPOSITORIES: biostudies-literature