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Impaired
Wound Repair and Delayed Angiogenesis in Aged Mice |
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Mari E. Swift,
Hynda K. Kleinman, and Luisa A. DiPietro |
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Department
of Microbiology and Immunology (MES, LAD), Burn and Shock Trauma Institute,
and Department of Surgery (LAD), Loyola University Medical Center, Maywood,
Illinois; and the National Institute of Dental and Craniofacial Research
(HKK), National Institutes of Health, Bethesda, Maryland |
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SUMMARY: Wound repair is
a multistep process consisting of hemostasis, inflammatory cell infiltration,
tissue regrowth, and remodeling. In aged individuals, this progression of
events is altered, resulting in wounds that heal more slowly than wounds
in the young. These studies were designed to examine the proliferative phase
of repair in young and aged mice, with attention to the angiogenic process.
Using a standardized excisional injury model, wound re-epithelialization,
collagen accumulation, and angiogenesis were examined. Re-epithelialization
and collagen synthesis were substantially delayed in aged mice as compared
with young mice. Angiogenesis in wounds from aged mice was also delayed,
with significantly more capillary growth in wounds from young mice than
aged mice. In addition, wounds from aged mice contained significantly less
of the angiogenic mediators fibroblast growth factor-2 (FGF-2) and vascular
endothelial growth factor (VEGF) than wounds from young animals (p <
0.05). Because macrophages are a rich source of angiogenic factors in wounds,
macrophage production of VEGF was examined. Macrophages from aged mice produced
significantly less VEGF than cells from young mice. To examine the in vivo
endothelial cell responsiveness, a defined amount of rFGF-2 was suspended
in Matrigel and placed subcutaneously in either young or aged mice. In response
to FGF-2, capillary growth into Matrigel was significantly less in aged
than young mice. The results suggest that a decline in angiogenic growth
factor production, as well as a decline in endothelial responsiveness to
specific factors, may account for the delayed wound angiogenesis 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. |
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