High-altitude rodents have abundant collaterals that protect against tissue injury after cerebral, coronary and peripheral artery occlusion

Abstract

Collateral number/density varies widely in brain and other tissues among strains of Mus musculus mice due to differences in genetic background. Recent studies have shown that prolonged exposure to reduced atmospheric oxygen induces additional collaterals to form, suggesting that natural selection may favor increased collaterals in populations native to high-altitude. High-altitude guinea pigs ( Cavia) and deer mice ( Peromyscus) were compared with lowland species of Peromyscus, Mus and Rattus (9 species/strains examined). Collateral density, diameter and other morphometrics were measured in brain where, importantly, collateral abundance reflects that in other tissues of the same individual. Guinea pigs and high-altitude deer mice had a greater density of pial collaterals than lowlanders. Consistent with this, guinea pigs and highlander mice evidenced complete and 80% protection against stroke, respectively. They also sustained significantly less ischemia in heart and lower extremities after arterial occlusion. Vessels of the circle of Willis, including the communicating collateral arteries, also exhibited unique features in the highland species. Our findings support the hypothesis that species native to high-altitude have undergone genetic selection for abundant collaterals, suggesting that besides providing protection in obstructive disease, collaterals serve a physiological function to optimize oxygen delivery to meet oxygen demand when oxygen is limiting.