PECAM-1 is necessary for flow-induced vascular remodeling.
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.


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 NFkappaB 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 NFkappaB 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.
Chen
Zhongming
Z
Department of Cell and Molecular Physiology, University of North Carolina at Chapel Hill, NC 27599, USA.
Tzima
Ellie
E
D000818:Animals; D017536:Carotid Artery, Common / Q000503:physiopathology*; D002478:Cells, Cultured; D023903:Coronary Restenosis / Q000503:physiopathology; D042783:Endothelial Cells / Q000502:physiology*; D018056:Hemorheology / Q000502:physiology*; D007249:Inflammation / Q000503:physiopathology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000502:physiology*; D015398:Signal Transduction; D017539:Tunica Intima / Q000293:injuries / Q000503:physiopathology*; D017540:Tunica Media / Q000293:injuries / Q000503:physiopathology
D019408:Platelet Endothelial Cell Adhesion Molecule-1