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Blood, 1 March 2007, Vol. 109, No. 5, pp. 1945-1952. Prepublished online as a Blood First Edition Paper on November 2, 2006; DOI 10.1182/blood-2006-08-041368. This Article Full Text (PDF) Supplemental Figures All Versions of this Article: blood-2006-08-041368v1 109/5/1945    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Isenberg, J. S Articles by Roberts, D. D. Search for Related Content PubMed PubMed Citation Articles by Isenberg, J. S Articles by Roberts, D. D. Related Collections Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted August 14, 2006 Accepted October 20, 2006 Thrombospondin-1 limits ischemic tissue survival by inhibiting nitric oxide-mediated vascular smooth muscle relaxation Jeff S Isenberg, Fuminori Hyodo, Ken-Ichiro Matsumoto, Martin J Romeo, Mones Abu-Asab, Maria Tsokos, Periannan Kuppusamy, David A Wink, Murali C Krishna, and David D. Roberts* Center for Cancer Research, National Cancer Institute, NIH Dept of Internal Medicine, Ohio State University NIH * Corresponding author; email: droberts{at}helix.nih.gov. The nitric oxide (NO)/cGMP pathway, by relaxing vascular smooth muscle cells, is a major physiological regulator of tissue perfusion. We now identify thrombospondin-1 as a potent antagonist of NO for regulating F-actin assembly and myosin light chain phosphorylation in vascular smooth muscle cells. Thrombospondin-1 prevents NO-mediated relaxation of pre-contracted vascular smooth muscle cells in a collagen matrix. Functional magnetic resonance imaging demonstrated that an NO-mediated increase in skeletal muscle perfusion was enhanced in thrombospondin-1 null relative to wild type mice, implicating endogenous thrombospondin-1 as a physiological antagonist of NO-mediated vasodilation. Using a random myocutaneous flap model for ischemic injury, tissue survival was significantly enhanced in thrombospondin-1 null mice. Improved flap survival correlated with increased recovery of oxygen levels in the ischemic tissue of thrombospondin-1 null mice as measured by electron paramagnetic resonance oximetry. These findings demonstrate an important antagonistic relationship between NO/cGMP signaling and thrombospondin-1 in vascular smooth muscle cells to regulate vascular tone and tissue perfusion. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: Thrombospondin says no to NO Themis R. Kyriakides Blood 2007 109: 1793. [Full Text] [PDF] This article has been cited by other articles: J. B. Maxhimer, D. R. Soto-Pantoja, L. A. Ridnour, H. B. Shih, W. G. DeGraff, M. Tsokos, D. A. Wink, J. S. Isenberg, and D. D. Roberts Radioprotection in Normal Tissue and Delayed Tumor Growth by Blockade of CD47 Signaling Science Translational Medicine, October 21, 2009; 1(3): 3ra7 - 3ra7. [Abstract] [Full Text] [PDF] J. S. Isenberg, D. S. Annis, M. L. Pendrak, M. Ptaszynska, W. A. Frazier, D. F. Mosher, and D. D. Roberts Differential Interactions of Thrombospondin-1, -2, and -4 with CD47 and Effects on cGMP Signaling and Ischemic Injury Responses J. Biol. Chem., January 9, 2009; 284(2): 1116 - 1125. [Abstract] [Full Text] [PDF] J. S. Isenberg, J. B. Maxhimer, F. Hyodo, M. L. Pendrak, L. A. Ridnour, W. G. DeGraff, M. Tsokos, D. A. Wink, and D. D. Roberts Thrombospondin-1 and CD47 Limit Cell and Tissue Survival of Radiation Injury Am. J. Pathol., October 1, 2008; 173(4): 1100 - 1112. [Abstract] [Full Text] [PDF] M. M. Krady, J. Zeng, J. Yu, S. MacLauchlan, E. A. Skokos, W. Tian, P. Bornstein, W. C. Sessa, and T. R. Kyriakides Thrombospondin-2 Modulates Extracellular Matrix Remodeling during Physiological Angiogenesis Am. J. Pathol., September 1, 2008; 173(3): 879 - 891. [Abstract] [Full Text] [PDF] J. S. Isenberg, D. D. Roberts, and W. A. Frazier CD47: A New Target in Cardiovascular Therapy Arterioscler Thromb Vasc Biol, April 1, 2008; 28(4): 615 - 621. [Abstract] [Full Text] [PDF] J. S. Isenberg, M. J. Romeo, C. Yu, C. K. Yu, K. Nghiem, J. Monsale, M. E. Rick, D. A. Wink, W. A. Frazier, and D. D. Roberts Thrombospondin-1 stimulates platelet aggregation by blocking the antithrombotic activity of nitric oxide/cGMP signaling Blood, January 15, 2008; 111(2): 613 - 623. [Abstract] [Full Text] [PDF] J. S. Isenberg, F. Hyodo, L. K. Pappan, M. Abu-Asab, M. Tsokos, M. C. Krishna, W. A. Frazier, and D. D. Roberts Blocking Thrombospondin-1/CD47 Signaling Alleviates Deleterious Effects of Aging on Tissue Responses to Ischemia Arterioscler Thromb Vasc Biol, December 1, 2007; 27(12): 2582 - 2588. [Abstract] [Full Text] [PDF] J. Ma and D. J. Waxman Collaboration between hepatic and intratumoral prodrug activation in a P450 prodrug-activation gene therapy model for cancer treatment Mol. Cancer Ther., November 1, 2007; 6(11): 2879 - 2890. [Abstract] [Full Text] [PDF] O. I. Stenina, E. J. Topol, and E. F. Plow Thrombospondins, Their Polymorphisms, and Cardiovascular Disease Arterioscler Thromb Vasc Biol, September 1, 2007; 27(9): 1886 - 1894. [Abstract] [Full Text] [PDF]

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