Gastric mucosa of aging individuals exhibits increased susceptibility to injury 
and delayed healing. Our previous studies in young rats showed that healing of 
mucosal injury depends on and is critically dependent on VEGF and angiogenesis. 
Since angiogenesis in aging gastric mucosa has not been examined before, in this 
study we examined the extent to which angiogenesis is impaired in gastric mucosa 
of aging vs. young rats and determined the underlying mechanisms with a focus on 
mucosal expression of VEGF (proangiogenic factor) and endostatin (antiangiogenic 
factor). Aging rats had significantly impaired gastric angiogenesis by ~12-fold, 
5-fold, 4-fold, and 3-fold, respectively (vs. young rats; all P < 0.001) at 24, 
48, 72, and 120 h following ethanol-induced gastric injury and reduced and 
delayed healing of mucosal erosions. In gastric mucosa of aging (vs. young) rats 
at baseline, VEGF expression was significantly reduced, whereas endostatin 
levels were significantly increased (P < 0.05 and P < 0.01, respectively). In 
contrast to young rats, gastric mucosal VEGF levels did not increase following 
ethanol-induced injury in aging rats. MMP-9 enzyme activity was significantly 
higher in gastric mucosa of aging vs. young rats both at baseline (2.7-fold) and 
24 h (3.8-fold) after ethanol injury (both P < 0.001). Since endostatin is 
generated from collagen XVIII by MMP-9, this finding can explain the mechanism 
of increased endostatin expression in aging gastric mucosa. The above findings 
demonstrate that reduced VEGF and increased endostatin result in the impaired 
angiogenesis and delayed injury healing in gastric mucosa of aging rats.