Impaired wound repair and delayed angiogenesis in aged mice

Wound repair is a multistep process consisting of hemostasis, inflammatory cell infiltration, tissue regrowth, and remodeling. In aged individuals, th is progression of events is altered, resulting in wounds that heal more slo wly than wounds in the young. These studies were designed to examine the pr oliferative phase of repair in young and aged mice, with attention to the a ngiogenic process. Using a standardized excisional injury model, wound re-e pithelialization, collagen accumulation, and angiogenesis were examined. Re -epithelialization and collagen synthesis were substantially delayed in age d mice as compared with young mice. Angiogenesis in wounds from aged mice w as also delayed, with significantly more capillary growth in wounds from yo ung mice than aged mice. In addition, wounds from aged mice contained signi ficantly less of the angiogenic mediators fibroblast growth factor-2 (FGF-2 ) and vascular endothelial growth factor (VEGF) than wounds from young anim als (p < 0.05). Because macrophages are a rich source of angiogenic factors in wounds, macrophage production of VEGF was examined. Macrophages from ag ed mice produced significantly less VEGF than cells from young mice. To exa mine the in vivo endothelial cell responsiveness, a defined amount of rFGF- 2 was suspended in Matrigel and placed subcutaneously in either young or ag ed mice. In response to FGF-2, capillary growth into Matrigel was significa ntly less in aged than young mice. The results suggest that a decline in an giogenic growth factor production, as well as a decline in endothelial resp onsiveness to specific factors, may account for the delayed wound angiogene sis in aged mice. These results also indicate that age-related alterations in macrophage function might partially account for the overall delay in the wound repair process.