Despite normal arteriogenic and angiogenic responses, hind limb perfusion recovery and necrotic and fibroadipose tissue clearance are impaired in matrix metalloproteinase 9-deficient mice

Asymptomatic peripheral arterial disease can be attributed to endogenous compensation for widespread occlusions, including the luminal growth of collateral arteries (ie, arteriogenesis), capillary network expansion by angiogenesis, and the repair of ischemically injured tissue. Here, we examined the relative roles of these three processes in establishing reperfusion by using models involving matrix metalloproteinase 9. Mice with matrix metalloproteinase 9-deficient bone marrow-derived cells exhibited impaired reperfusion; however, neither angiogenesis nor arteriogenesis was affected. Instead, impaired reperfusion was strongly correlated with high necrotic and fibroadipose tissue composition, stressing the importance of stimulating concomitant muscle repair in therapeutic revascularization strategies.