Published online before print January 20, 2005, doi: 10.1161/01.RES.0000156903.37007.d1
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Submitted on June 24, 2004
Revised on January 11, 2005
Accepted on January 12, 2005
Central Role of PKC
in Neointimal Expansion Triggered by Acute Arterial Injury
Martin Andrassy ;
From the Departments of Surgery (M.A., D.B., E.H., Y.S.Z., A.M.S., S.-F.Y.) and Pathology (S.D.Y.), College of Physicians and Surgeons, Columbia University, New York; Max Planck Institute of Experimental Endocrinology (M.L.), Hannover, Germany; and the Departments of Cardiology (H.A.K.) and Medicine (P.P.N.), University of Heidelberg, Heidelberg, Germany.
* To whom correspondence should be addressed. E-mail: sy18{at}columbia.edu.
We tested the hypothesis that PKC
contributes to vascular smooth muscle cell (SMC) migration and proliferation; processes central to the pathogenesis of restenosis consequent to vascular injury. Homozygous PKC null (-/-) mice or wild-type mice fed the PKC inhibitor, ruboxistaurin, displayed significantly decreased neointimal expansion in response to acute femoral artery endothelial denudation injury compared with controls. In vivo and in vitro analyses demonstrated that PKCII is critically linked to SMC activation, at least in part via regulation of ERK1/2 MAP kinase and early growth response-1. These data highlight novel roles for PKC in the SMC response to acute arterial injury and suggest that blockade of PKC may represent a therapeutic strategy to limit restenosis.
Key words: arterial injury • PKC
•
smooth muscle cell activation •
inhibitor •
neointima
This article has been cited by other articles:
 |
|
 |
|
  T. S. Monahan, N. D. Andersen, M. C. Martin, J. Y. Malek, G. V. Shrikhande, L. Pradhan, C. Ferran, and F. W. LoGerfo MARCKS silencing differentially affects human vascular smooth muscle and endothelial cell phenotypes to inhibit neointimal hyperplasia in saphenous vein FASEB J, February 1, 2009; 23(2): 557 - 564. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. S. Chang, T. Wendt, W. Qu, L. Kong, Y. S. Zou, A. M. Schmidt, and S.-F. Yan Oxygen Deprivation Triggers Upregulation of Early Growth Response-1 by the Receptor for Advanced Glycation End Products Circ. Res., April 25, 2008; 102(8): 905 - 913. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Kong, M. Andrassy, J. S. Chang, C. Huang, T. Asai, M. J. Szabolcs, S. Homma, R. Liu, Y. S. Zou, M. Leitges, et al. PKC{beta} modulates ischemia-reperfusion injury in the heart Am J Physiol Heart Circ Physiol, April 1, 2008; 294(4): H1862 - H1870. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. C. Spalding, R. Watson, M. E. Davis, A. C. Kim, T. S. Lawrence, and E. Ben-Josef Inhibition of Protein Kinase C{beta} by Enzastaurin Enhances Radiation Cytotoxicity in Pancreatic Cancer Clin. Cancer Res., November 15, 2007; 13(22): 6827 - 6833. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Xia, H. Wang, S. Munk, H. Frecker, H. J. Goldberg, I. G. Fantus, and C. I. Whiteside Reactive oxygen species, PKC-beta1, and PKC-{zeta} mediate high-glucose-induced vascular endothelial growth factor expression in mesangial cells Am J Physiol Endocrinol Metab, November 1, 2007; 293(5): E1280 - E1288. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Hosoda, M. Hiroyama, A. Sanbe, J.-i. Birumachi, T. Kitamura, S. Cotecchia, P. C. Simpson, G. Tsujimoto, and A. Tanoue Blockade of both {alpha}1A- and {alpha}1B-adrenergic receptor subtype signaling is required to inhibit neointimal formation in the mouse femoral artery Am J Physiol Heart Circ Physiol, July 1, 2007; 293(1): H514 - H519. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S.-F. Yan, E. Harja, M. Andrassy, T. Fujita, and A. M. Schmidt Protein Kinase C {beta}/Early Growth Response-1 Pathway: A Key Player in Ischemia, Atherosclerosis, and Restenosis J. Am. Coll. Cardiol., October 27, 2006; 48(9_Suppl_A): A47 - A55. [Abstract] [Full Text] [PDF]
|
|