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Increased Ischemic Tissue Survival through Targeting Thrombospondin‐1
Author(s) -
Isenberg Jeffrey S,
Romeo Martin,
AbuAsab Mones,
Tsokas Maria,
Frazier William A,
Roberts David D
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.5.a11-b
Subject(s) - cd47 , ischemia , perfusion , endogeny , wound healing , vasodilation , nitric oxide , medicine , thrombospondin 1 , necrosis , vascular smooth muscle , pharmacology , cancer research , receptor , immunology , angiogenesis , smooth muscle
Tissue survival requires sustained perfusion. Ischemia secondary to surgery or trauma can limit soft tissue survival, resulting in tissue necrosis and delayed wound healing. Therapeutic interventions to increase soft tissue perfusion have to date met with limited success. The bioactive gas nitric oxide (NO), which is produced by vascular endothelial cells constitutively, can rapidly dilate arteries and increase tissue perfusion. However, under ischemic conditions endogenous NO is insufficient to prevent tissue necrosis. We recently discovered that endogenous thrombospondin‐1 (TSP1) is a potent antagonist of NO‐induced vasodilation. TSP1 released by activated platelets and produced by vascular cells potently blocks NO driven relaxation of vascular smooth muscle cells at the level of soluble guanylate cyclase via its receptor CD47. In the absence of TSP1 or CD47, survival of ischemic injury is dramatically increased. We are investigating therapeutic approaches to target TSP1 or CD47 to increase wound healing under conditions of ischemia.