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Publication : Increasing survival of ischemic tissue by targeting CD47.

First Author  Isenberg JS Year  2007
Journal  Circ Res Volume  100
Issue  5 Pages  712-20
PubMed ID  17293482 Mgi Jnum  J:133700
Mgi Id  MGI:3783953 Doi  10.1161/01.RES.0000259579.35787.4e
Citation  Isenberg JS, et al. (2007) Increasing survival of ischemic tissue by targeting CD47. Circ Res 100(5):712-20
abstractText  Thrombospondin-1 (TSP1) limits the angiogenic and vasodilator activities of NO. This activity of TSP1 can be beneficial in some disease states, but endogenous TSP1 limits recovery of tissue perfusion following fixed ischemic injury in dorsal skin flaps in mice. Using mice lacking the TSP1 receptors CD36 or CD47, we now show that CD47 is the necessary receptor for limiting NO-mediated vascular smooth muscle relaxation and tissue survival following ischemic injury in skin flaps and hindlimbs. We further show that blocking CD47 or TSP1 using monoclonal antibodies and decreasing CD47 expression using an antisense morpholino oligonucleotide are effective therapeutic approaches to dramatically increase survival of soft tissue subjected to fixed ischemia. These treatments facilitate rapid vascular remodeling to restore tissue perfusion and increase skin and muscle viability. Thus, limiting CD47-dependent antagonism of NO-mediated vasodilation and vascular remodeling is a promising therapeutic modality to preserve tissues subject to ischemic stress.
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