X-Message-Number: 24949
Date: Sat, 30 Oct 2004 12:08:32 -0700 (PDT)
From: Doug Skrecky <>
Subject: aging impairs VEGF & wound repair

Lab Invest. 1999 Dec;79(12):1479-87
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, 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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