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(Circulation Research. 2008;103:1053.)
© 2008 American Heart Association, Inc.

Editorials

Counterbalancing Forces

What Is Thrombospondin-1 Doing in Atherosclerotic Lesions?

Olga I. Stenina, Edward F. Plow

From the Joseph J. Jacobs Center for Thrombosis and Vascular Biology, Department of Molecular Cardiology, Cleveland Clinic, Ohio.

Correspondence to Edward F. Plow, PhD, Department of Molecular Cardiology, Cleveland Clinic, 9500 Euclid Ave, NB-50, Cleveland, OH 44195. E-mail plowe@ccf.org

See related article, pages 1181–1189

Key Words: thrombospondin-1 • atherosclerosis • macrophages • inflammation • apoE knockout

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

Since the discovery of thrombospondin (TSP)-1 thirty years ago,¹ this matricellular (regulating cell–matrix interaction) protein has been a focal point for attention of cardiovascular biologists. Initial studies of TSP-1 emphasized its role as a major constituent of platelet -granules and its involvement in platelet aggregation and thrombosis. However, it soon became clear that other cell types, eg, endothelial (ECs),² leukocytes, fibroblasts, and vascular smooth muscle cells (SMCs),^3–5 also produce and secrete TSP-1. This broad distribution triggered extensive studies of the influence of TSP-1 on cellular functions and documented numerous effects on blood and vascular cell responses. The breadth of its effects on cells results from the multidomain structure of TSP-1. The domains fold and often function independently, leading to cell type–specific effects that depend on the expression and combination of multiple receptors for TSP-1 on the cell surface and/or its multiple binding partners in the extracellular matrix. A major function of TSP-1 has emerged from among the myriad of its activities: TSP-1 is among the most potent antiangiogenic proteins and is a regulator of angiogenesis in tumors,⁶ thereby influencing tumor progression and aggressiveness. This effect of TSP-1 is ascribed to its induction of EC apoptosis mediated through interaction with CD36,^7,8 inhibition of EC migration,⁹ and the CD36-independent cycle arrest.¹⁰

The effects of TSP-1 on ECs could also be proatherogenic because of EC dysfunction and its consequences on blood cell recruitment at both initial and advanced stages of plaque development. Proatherogenic effect of TSP-1 also could arise from its effects on . . . [Full Text of this Article]

Related Article:

Thrombospondin-1 Deficiency Accelerates Atherosclerotic Plaque Maturation in ApoE^–/– Mice

Rute Moura, Marc Tjwa, Petra Vandervoort, Soetkin Van kerckhoven, Paul Holvoet, and Marc F. Hoylaerts
Circ. Res. 2008 103: 1181-1189. [Abstract] [Full Text] [PDF]