Impaired angiogenesis in aging is associated with alterations in vessel density, matrix composition, inflammatory response, and growth factor expression

J Histochem Cytochem. 2003 Sep;51(9):1119-30. doi: 10.1177/002215540305100902.

Abstract

It is generally accepted that angiogenesis is delayed in aging. To define the effects of age on the neovascular response, polyvinyl alcohol sponges were implanted SC in young (6-8 months old, n=11) and aged (23-25 months old, n=13) mice and sampled at 14 and 19 days. Angiogenic invasion was significantly delayed in aged mice at 14d relative to young at 14d (% area of invasion 9.0 +/- 3.7 vs 19.0 +/- 5.6; p=0.02). Although microvessel morphology and basement membrane composition were similar between the age groups, a significant decrease in capillary density was noted in aged tissues at 14d (7.5 +/- 4.1) and 19d (12.1 +/- 2.8) relative to young at 14d (18.7 +/- 2.3) (p<0.01 A14d vs Y14d). In comparison to young at 14d, the inflammatory response was decreased by 43 +/- 2.9% and 36 +/- 7.8% in aged mice at 14d and 19d, respectively. Tissues of aged mice showed less newly deposited collagen. There was a lack of expression of transforming growth factor-beta1 (TGF-beta1) and vascular endothelial growth factor (VEGF) in aged mice at 14d (0.63 +/- 0.3) and 19d (1.14 +/- 0.5) vs young at 14d (1.92 +/- 0.5) (p< or =0.01 A14d vs Y14d for VEGF). However, similar production of VEGF receptor2 was observed. In contrast to young mice, there was significantly increased expression of thrombospondin-2 (TSP-2) in aged mice from 14d (14.6 x 10(3) +/- 7.3 x 10(3)) to 19d (34.9 x 10(3) +/- 17 x 10(3)). We conclude that angiogenesis in aging is not merely delayed, but is altered due to multiple impairments.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Aging / metabolism
  • Aging / physiology*
  • Animals
  • Basement Membrane / metabolism
  • Blood Vessels* / cytology
  • Blood Vessels* / metabolism
  • Capillaries / cytology
  • Capillaries / metabolism
  • Cell Division
  • Collagen / metabolism
  • Endothelial Growth Factors / metabolism
  • Growth Substances / metabolism*
  • Immunohistochemistry
  • Inflammation / metabolism
  • Inflammation / pathology
  • Intercellular Signaling Peptides and Proteins / metabolism
  • Lymphokines / metabolism
  • Macrophages / pathology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Inbred DBA
  • Monocytes / pathology
  • Neovascularization, Physiologic*
  • Thrombospondins / metabolism
  • Vascular Endothelial Growth Factor A
  • Vascular Endothelial Growth Factor Receptor-2 / metabolism
  • Vascular Endothelial Growth Factors

Substances

  • Endothelial Growth Factors
  • Growth Substances
  • Intercellular Signaling Peptides and Proteins
  • Lymphokines
  • Thrombospondins
  • Vascular Endothelial Growth Factor A
  • Vascular Endothelial Growth Factors
  • thrombospondin 2
  • Collagen
  • Vascular Endothelial Growth Factor Receptor-2