Journals of Gerontology Series A: Biological Sciences and Medical Sciences Large Type Edition
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]
Author:
 		Keyword(s):
Year:  Vol:  Page: 

This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow Cited by other online articles
Google Scholar
Right arrow Articles by Koike, T.
Right arrow Articles by Reed, M. J.
Right arrow Articles citing this Article
PubMed
Right arrow PubMed Citation
Right arrow Articles by Koike, T.
Right arrow Articles by Reed, M. J.
The Journals of Gerontology Series A: Biological Sciences and Medical Sciences 58:B798-B805 (2003)
© 2003 The Gerontological Society of America

Inhibited Angiogenesis in Aging: A Role for TIMP-2

Teruhiko Koike1, Robert B. Vernon2, Michel D. Gooden2, Eman Sadoun1 and May J. Reed1

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: (Search Google Scholar for Other Citing Articles)


Home page
 SCI AGING KNOWL ENVIRONHome page
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]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
All GSA journals The Gerontologist
Journals of Gerontology Series B: Psychological Sciences and Social Sciences
Copyright © 2003 by The Gerontological Society of America.