Collateral density, remodeling and VEGF‐A expression differ widely between mouse strains.

Collateral density and ischemia‐induced collateral growth vary greatly among species. To explore underlying mechanisms, which are unknown, we characterized two mouse strains with marked differences in both parameters. Immediately after femoral artery ligation, adductor and foot perfusion were lower in BALB/c (BC) than C57BL/6 (B6) mice (P<0.05 here and below), suggesting fewer collaterals. Angiography and histology confirmed 35% fewer collaterals in BC thigh. Perfusion recovery was lower in BC, in association with 54% less collateral remodeling, reduced angiogenesis, greater ischemia and impaired limb use. Recruitment of CD45+ and CD4+ leukocytes to collaterals was similar between strains despite 50% less TNF‐α expression in BC. In normal tissues, compared to B6, BC have an altered arterial branching pattern, and like skeletal muscle, have 30% fewer collaterals in intestine, and remarkably, almost none in the pial circulation, resulting in greatly impaired perfusion after cerebral artery ligation. Moreover, VEGF‐A expression, which is critical in embryonic vascular patterning, was strongly reduced in adult BC. Interestingly, BC are born with ~50% fewer collaterals that are lost by 3 weeks, suggesting failure in collateral maturation. These findings suggest these strains offer a model to examine genetic determinants of variation in collateral formation and growth in ischemia.