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Published Online
on December 20, 2007

Arteriosclerosis, Thrombosis, and Vascular Biology. 2007
Published online before print December 20, 2007, doi: 10.1161/ATVBAHA.107.156810
A more recent version of this article appeared on March 1, 2008
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Submitted on September 26, 2007
Accepted on December 10, 2007

CaMKII-{delta} Isoform Regulation of Neointima Formation After Vascular Injury

Suzanne J. House and Harold A. Singer *

From the Center for Cardiovascular Sciences, Albany Medical College (MC-8), Albany, NY.

* To whom correspondence should be addressed. E-mail: singerh{at}mail.amc.edu.

Objective—The purpose of this study was to test the function of the calcium/calmodulin-dependent protein kinase II {delta}2 isoform (CaMKII{delta}2) in regulating vascular smooth muscle (VSM) cell proliferation and migration in response to vascular injury.

Methods and Results—CaMKII isoform content was assessed in rat carotid arteries after balloon angioplasty–induced injury by Western blotting with isoform specific antibodies. Within 3 days after injury, a significant increase in CaMKII{delta}2 and decrease in CaMKII{gamma} isoform content was observed in both medial smooth muscle and adventitial fibroblasts. Neointimal VSM cells expressed primarily the {delta}2 isoform. Incubation of the injured vessel with adenovirus encoding siRNA targeting CaMKII{delta} isoforms prevented upregulation of the {delta}2 isoform in the media and adventitia; inhibited cell proliferation assessed by PCNA expression in both layers and markedly inhibited neointima formation and adventitial thickening.

Conclusions—CaMKII{delta}2 is specifically induced in VSM and adventitial fibroblasts during the response of an artery to injury and is a positive regulator of proliferation and migration in the vessel wall contributing to neointima formation and vascular remodeling. This provides a potential mechanism for Ca2+-dependent regulation of VSM and myofibroblast proliferation and migration in response to vascular injury or disease.


Key words: CaMKII • VSM proliferation • vascular injury • restenosis • neointima




This article has been cited by other articles:


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Am. J. Physiol. Cell Physiol.Home page
M. Z. Mercure, R. Ginnan, and H. A. Singer
CaM kinase II{delta}2-dependent regulation of vascular smooth muscle cell polarization and migration
Am J Physiol Cell Physiol, June 1, 2008; 294(6): C1465 - C1475.
[Abstract] [Full Text] [PDF]