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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2002;22:1522.)
© 2002 American Heart Association, Inc.

Editorials

PAI-1 and Cellular Migration

Dabbling in Paradox

Douglas E. Vaughan

From the Division of Cardiovascular Medicine, Vanderbilt University Medical Center, Nashville, Tenn.

Correspondence to Douglas E. Vaughan, MD, Division of Cardiovascular Medicine, Vanderbilt University Medical Center, Nashville, TN 37232. E-mail doug.Vaughan@mcmail.vanderbilt.edu

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

"Do not dabble in paradox, it puts you in danger of fortuitous wit."

— T. Stoppard, Arcadia, 1995

The migration of vascular smooth muscle cells (SMCs) plays an important role in the response to vascular injury and in atherosclerosis. In fact, the focal accumulation of smooth muscle in the arterial intima is thought to make a critical contribution to the formation of vascular lesions. Smooth muscle migration is a complex process that requires a stimulus and a matrix substratum that facilitates cell adhesion and movement. Cells attach via specific integrin receptors that bind to the matrix, thereby providing "traction" for cells and the necessary engagement of intercellular micromotors that drive cell movement.

See page 1573

Based on observations originally made in genetically modified mice, a role for plasminogen activator inhibitor-1 (PAI-1) on cellular migration was suggested.¹ Urokinase-type plasminogen activator (u-PA)–deficient mice exhibit a reduced neointimal response to injury. In contrast, PAI-1–deficient mice show an exaggerated neointimal response to injury while adenoviral-delivered PAI-1 overexpression inhibits vascular wound healing and neointima formation. Since PAI-1 plays as a direct and fast-acting inhibitor of u-PA, it was argued that these observations could be explained by enhanced matrix degradation and accelerated cell migration in the absence of PAI-1. Subsequently, Stefansson and Lawrence² showed that active PAI-1 directly impairs SMC adhesion and migration by limiting the binding of vitronectin to the integrin receptor _vß₃. PAI-1 probably also impairs cell adhesion and migration by competitively inhibiting the binding of the u-PA receptor to vitronectin. If the . . . [Full Text of this Article]

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