Microvascular dynamics regulate post-ischemic muscle damage and regeneration in experimental hindlimb ischemia
Research Square (Research Square)(2023)
Abstract
Abstract Tissue microvasculature is known to remodel in response to ischemia. Yet, how this remodeling contributes to the process of post-ischemic recovery is still not completely understood. We studied how microvascular changes relate to post-ischemic muscle repair. Muscle-level microvascular alterations of blood flow and hemoglobin oxygenation, and post-ischemic myofiber and capillary responses were analyzed in aged, healthy C57Bl/6J mice (n = 48) and aged, hyperlipidemic LDLR −/− ApoB 100/100 mice (n = 69) after induction of acute hindlimb ischemia using contrast ultrasound, photoacoustic imaging, and histological analyses, respectively. Microvascular responses leading to successful post-ischemic muscle repair in C57Bl/6J mice included an early capillary dilation phase preceding the return of arterial driving pressure followed by an increase in capillary density that further supported satellite cell-induced muscle regeneration. Failure of initial capillary enlargement due to a life-long moderate hypercholesterolemia in LDLR −/− ApoB 100/100 mice led to inability to recover arterial driving pressure and resulted in an increase in distal necrosis, chronic tissue damage and a delay in overall recovery after ischemia. To conclude, these data reveal the important role of transient capillary enlargement in initiating a cascade of capillary events that are crucial for a successful post-ischemic muscle recovery. Essentially, the observed dynamic nature of the post-ischemic capillaries should be considered when designing novel treatments targeting the microvasculature in ischemic diseases.
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Key words
ischemia,muscle,regeneration,post-ischemic
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