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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2009;29:1067.)
© 2009 American Heart Association, Inc.

Integrative Physiology/Experimental Medicine

PECAM-1 Is Necessary for Flow-Induced Vascular Remodeling

Zhongming Chen; Ellie Tzima

From the Department of Cell and Molecular Physiology (Z.C., E.T.) and the Carolina Cardiovascular Biology Center (E.T.), University of North Carolina at Chapel Hill.

Correspondence to Ellie Tzima, PhD, Department of Cell and Molecular Physiology, CB7545, 6341C MBRB, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599. E-mail etzima{at}med.unc.edu

Objective— Vascular remodeling is a physiological process that occurs in response to long-term changes in hemodynamic conditions, but may also contribute to the pathophysiology of intima-media thickening (IMT) and vascular disease. Shear stress detection by the endothelium is thought to be an important determinant of vascular remodeling. Previous work showed that platelet endothelial cell adhesion molecule-1 (PECAM-1) is a component of a mechanosensory complex that mediates endothelial cell (EC) responses to shear stress.

Methods and Results— We tested the hypothesis that PECAM-1 contributes to vascular remodeling by analyzing the response to partial carotid artery ligation in PECAM-1 knockout mice and wild-type littermates. PECAM-1 deficiency resulted in impaired vascular remodeling and significantly reduced IMT in areas of low flow. Inward remodeling was associated with PECAM-1-dependent NFB activation, surface adhesion molecule expression, and leukocyte infiltration as well as Akt activation and vascular cell proliferation.

Conclusions— PECAM-1 plays a crucial role in the activation of the NFB and Akt pathways and inflammatory cell accumulation during vascular remodeling and IMT. Elucidation of some of the signals that drive vascular remodeling represent pharmacologically tractable targets for the treatment of restenosis after balloon angioplasty or stent placement.

Key Words: hemodynamics • vascular remodeling • intima-media thickening • inflammation