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(Hypertension. 2004;44:809.)
© 2004 American Heart Association, Inc.

Editorial Commentaries

Osteopontin: A Protective Mediator of Cardiac Fibrosis?

From the Department of Medicine/Cardiology, Deutsches Herzzentrum, Berlin, Germany.

Correspondence to Dr Kristof Graf, Department of Medicine/Cardiology, Deutsches Herzzentrum, Berlin Augustenburger Platz 1, Berlin, D-13353, Germany. E-mail graf@dhzb.de

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

Osteopontin (OP) is a multifunctional cytokine and adhesion protein that contains an RGD (arginin-glycin-aspartate) binding sequence that enables it to interact with several integrins, CD44 variants, and other adhesion receptors. OP receptor binding then directly or indirectly activates intracellular signaling pathways, mediating its effects on cell–matrix and cell–cell interactions. OP is increased in response to pro-inflammatory cytokines and mechanical strain in various cell types,¹ and the function of its secreted protein can be altered by proteases, including thrombin.² Thus, OP can exists as an immobilized matrix molecule (eg, in bone, atherosclerotic plaques, or calcified heart valves) or as soluble cytokine.

Cell signaling by OP is predominantly mediated through integrin engagement. Cleavage of OP by thrombin exposes integrin binding sites² (eg, for ₉ß₁), which are important for OP-mediated adhesion/migration. OP is chemotactic for various cell types, most notably monocytes/macrophages, which are attracted to sites of injury and inflammation. The best-characterized OP-induced signal pathway is the integrin-stimulated FAK-Src-Rho pathway in osteoclasts.¹ However, identification and dissection of signal transduction pathways are complicated by the fact that OP potentially binds to several cell surface receptors.

OP and the Heart

Proper organization of the extracellular matrix is required to maintain the integrity and organization of cardiac cells. Adaptive remodeling of the myocardium, caused by either increased workload or injury, requires mediators for the communication of cardiac cells with their surrounding extracellular matrix. This makes OP an ideal candidate. Various stimuli have been found to induce OP in cardiac cells, including fibroblasts,³ cardiomyocytes,^4,5 macrophages, endothelial cells, and vascular smooth . . . [Full Text of this Article]

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