Impaired Angiogenesis in Aging Is Associated with Alterations in Vessel Density, Matrix Composition, Inflammatory Response, and Growth Factor Expression

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-β1 (TGF-β1) 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≤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 × 103 ± 7.3 × 103) to 19d (34.9 × 103 ± 17 × 103). We conclude that angiogenesis in aging is not merely delayed, but is altered due to multiple impairments.