This Article Full Text Full Text (PDF) Services Download to citation manager Citing Articles Citing Articles via HighWire PubMed PubMed Citation

Inhibited Angiogenesis in Aging: A Role for TIMP-2

¹ Division of Gerontology and Geriatric Medicine, Department of Medicine, University of Washington, Seattle.
² Department of Vascular Biology, The Hope Heart Institute, Seattle, Washington.

Factors responsible for age-associated impairment of angiogenesis are poorly understood. We observed that in aged mice, new fibrovascular tissue within subcutaneous polyvinyl alcohol sponges expressed more tissue inhibitor of metalloproteinases (TIMP)-2 than did corresponding tissue from young mice. In complementary studies in vitro, we utilized young and aged human microvascular endothelial cell lines (hmEC36 and hmEC90, respectively) and compared their morphogenetic capacity within three-dimensional collagen. HmEC90 exhibited poor formation of tubular, capillary-like structures in vitro, diminished expression of active matrix metalloproteinase (MMP)-2, and similar or lesser amounts of MT1-MMP relative to hmEC36. Correspondingly, the MMP inhibitor GM6001 decreased tubulogenesis by hmEC36 to levels observed for hmEC90. In vitro, hmEC90 expressed similar quantities of TIMP-1, but more TIMP-2 than did hmEC36. Accordingly, purified TIMP-2 inhibited tubulogenesis by hmEC36. Collectively, our studies indicate that elevated levels of TIMP-2 modulate decreased angiogenesis in aged tissues, most likely via TIMP-2-mediated inhibition of MMP-2 and MT1-MMP.

This article has been cited by other articles:

				R. P. Brandes, I. Fleming, and R. Busse Endothelial aging Cardiovasc Res, May 1, 2005; 66(2): 286 - 294. [Abstract] [Full Text] [PDF]

				M. J. Reed and J. M. Edelberg Impaired Angiogenesis in the Aged Sci. Aging Knowl. Environ., February 18, 2004; 2004(7): pe7 - 7. [Abstract] [Full Text]