Cerebral angiogenesis and expression of angiogenic factors in aging rats after exercise

The effect that exercise has on angiogenesis in the aging rat is unknown. We initiated this study with the intent to determine if exercise could induce angiogenesis in aging rats, as well as in adult rats reported previously. The markers we used to determine our endpoint were vascular endothelial growth factor (VEGF) and angiopoietin 1 and 2, as well as vascular density. Aged (22 month old) female Fisher 344 rats (n=16) were exercised on a treadmill 30 minutes each day for 3 weeks, or housed as non-exercised controls for the same duration. At the end of the exercise protocol, a significant (p<0.01) increase in the density of microvessels was found within the cerebral vasculature of the rats. Exercise was also associated with a significantly (p<0.01) increased mRNA expression of angiopoietin 1 and 2 in the aged cohort of rats. A mild but significant (p<0.01) increase in the four isoforms of VEGF mRNA (120, 144, 164, 188) were observed, with VEGF120 and VEGF144 being more markedly up-regulated than the other two. VEGF protein expression was also significantly (p<0.01) increased. This study demonstrates that angiogenesis can be induced in aging rats via exercise. The induced angiogenesis was associated with overexpression of angiogenic factors. These results support the hypothesis that an angiogenic response to chronic physical exercise is maintained with aging.