title: 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-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.
authors.affiliation: Division of Gerontology and Geriatric Medicine, Department of Medicine, University of Washington, Seattle, Washington 98104, USA. mjr@u.washington.edu
authors.forename: Eman
authors.initials: E
authors.lastname: Sadoun
authors.forename: May J
authors.initials: MJ
authors.lastname: Reed
mesh_terms: D000375:Aging / Q000378:metabolism / Q000502:physiology*; D000818:Animals; D001485:Basement Membrane / Q000378:metabolism; D001808:Blood Vessels / Q000166:cytology / Q000378:metabolism; D002196:Capillaries / Q000166:cytology / Q000378:metabolism; D002455:Cell Division; D003094:Collagen / Q000378:metabolism; D016228:Endothelial Growth Factors / Q000378:metabolism; D006133:Growth Substances / Q000378:metabolism*; D007150:Immunohistochemistry; D007249:Inflammation / Q000378:metabolism / Q000473:pathology; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D008222:Lymphokines / Q000378:metabolism; D008264:Macrophages / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D009000:Monocytes / Q000473:pathology; D018919:Neovascularization, Physiologic; D019699:Thrombospondins / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism; D042442:Vascular Endothelial Growth Factors; D000099262:Thrombospondin 2
chemical_list: D003094:Collagen; D016228:Endothelial Growth Factors; D006133:Growth Substances; D036341:Intercellular Signaling Peptides and Proteins; D008222:Lymphokines; D019699:Thrombospondins; D042461:Vascular Endothelial Growth Factor A; D040301:Vascular Endothelial Growth Factor Receptor-2; D042442:Vascular Endothelial Growth Factors; D000099262:Thrombospondin 2