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(Circulation Research. 2007;100:602.)
© 2007 American Heart Association, Inc.

Editorials

Targeting CD47

NO Limit on Therapeutic Potential

David J. Kaczorowski, Timothy R. Billiar

From the Department of Surgery (D.J.K., T.R.B.), University of Pittsburgh, Pa.

Correspondence to Timothy R. Billiar, MD, Department of Surgery, University of Pittsburgh School of Medicine, 200 Lothrop Street, Presbyterian Hospital F1200, Pittsburgh, PA 15213. E-mail billiartr@upmc.edu

See related article, pages 712–720

Key Words: ischemia • thrombospondin-1 • CD-47 • nitric oxide • vascular endothelium

An extract of the first 250 words of the full text is provided, because this article has no abstract.

Thrombospondin-1 (TSP-1) is a homotrimeric glycoprotein with multiple functional domains that serves as a key mediator of a number of diverse cellular and physiologic processes.¹ TSP-1 is the major component of the granule of platelets. On stimulation by thrombin, TSP-1 is released and binds to the platelet surface. It then mediates platelet aggregation by crosslinking fibrinogen-GPIIb/IIIa complexes, which further secures platelets and tethers the thrombus.^2,3 Given its prominent role in thrombosis, it is not surprising that TSP-1 is also a key mediator of neointimal hyperplasia and vascular disease. TSP-1 is found in the lumen and media of diseased and injured vessels and anti-TSP-1 antibodies decrease neointimal hyperplasia in a carotid artery injury model.^4,5 Interestingly, a single nucleotide polymorphism in the TSP-1 gene may be associated with familial early myocardial infarctions.⁶ TSP-1 appears to play contradictory roles in angiogenesis, both stimulating neovascularization in conjunction with other factors, but also inhibiting the process via apoptosis of endothelial cells.^7,8 Acute regulation of tissue perfusion, ischemia/reperfusion, wound healing, and tumor growth and progression are other processes where TSP-1 also appears to play a prominent role.^9–13,13a

As there are multiple cell surface receptors for TSP-1, the diverse and sometimes dichotomous functions of TSP-1 may involve ligation of different receptors and combinations of receptors through its distinct domains. Heparan sulfate proteoglycans, ß1 integrins, LRP/calreticulin, CD36, and CD47 have been identified as mediators of the effects of TSP-1.^14–18 The ability to intervene on or manipulate any TSP-1 dependent pathway or process will ultimately depend on an understanding . . . [Full Text of this Article]

Related Article:

Increasing Survival of Ischemic Tissue by Targeting CD47

Jeff S. Isenberg, Martin J. Romeo, Mones Abu-Asab, Maria Tsokos, Anna Oldenborg, Loretta Pappan, David A. Wink, William A. Frazier, and David D. Roberts
Circ. Res. 2007 100: 712-720. [Abstract] [Full Text] [PDF]

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				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]