HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 287/2/H659    most recent 00162.2004v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (16) Citing Articles via Google Scholar Google Scholar Articles by Zhang, C. Articles by Jennings, L. K. Search for Related Content PubMed PubMed Citation Articles by Zhang, C. Articles by Jennings, L. K.

Attenuation of neointima formation through the inhibition of DNA repair enzyme PARP-1 in balloon-injured rat carotid artery

Vascular Biology Center of Excellence, Department of Medicine, University of Tennessee Health Science Center, Memphis, Tennesee 38163

Submitted 17 February 2004 ; accepted in final form 19 March 2004

Increased oxidative stress is a major characteristic of restenosis after angioplasty. The oxidative stress is mainly created by oxidants such as reactive oxygen species (ROS), which are assumed to play an important role in neointima formation after angioplasty. DNA is a sensitive target for oxidants; however, oxidative DNA damage remains a poorly examined field in the pathogenesis of restenosis. In the present study, we demonstrated that the expression of the oxidative DNA damage marker 7,8-dihydro-8-oxo-2'-deoxyguanosine (8-oxo-dG) was quickly increased in rat carotid arteries after balloon injury. It reached its peak at 14 days after injury and still kept high expression at 28 days after injury. The immunostaining of 8-oxo-dG was present predominantly in the neointima. In response to oxidative DNA damage, the DNA repair enzyme poly(ADP-ribose) polymerase-1 (PARP-1) was significantly increased after balloon injury. The time course change and location of PARP-1 is similar to that of 8-oxo-dG. Daily injections of the PARP-1 inhibitor PJ34 (5 mg·kg^–1·day^–1 ip) attenuated neointima formation by 40% at 7, 14, and 28 days after balloon injury. Treatment with PJ34 inhibited leukocyte infiltration and improved both anatomic (reendothelialization) and functional (endothelial function) recovery of endothelial cells after balloon injury. In conclusion, levels of oxidative DNA damage and the DNA repair enzyme PARP-1 are increased in vessels after balloon injury. Inhibition of PARP-1 attenuates neointima formation through inhibition of leukocyte infiltration and improvement of endothelial cell recovery after balloon injury. Targeting of the DNA repair enzyme might be a therapeutic strategy for restenosis.

angioplasty; DNA damage; oxidative stress; restenosis

This article has been cited by other articles:

				R. Ji, Y. Cheng, J. Yue, J. Yang, X. Liu, H. Chen, D. B. Dean, and C. Zhang MicroRNA Expression Signature and Antisense-Mediated Depletion Reveal an Essential Role of MicroRNA in Vascular Neointimal Lesion Formation Circ. Res., June 8, 2007; 100(11): 1579 - 1588. [Abstract] [Full Text] [PDF]

				J. Yang, Y. Cheng, R. Ji, and C. Zhang Novel model of inflammatory neointima formation reveals a potential role of myeloperoxidase in neointimal hyperplasia Am J Physiol Heart Circ Physiol, December 1, 2006; 291(6): H3087 - H3093. [Abstract] [Full Text] [PDF]

				J.-H. Parmentier, C. Zhang, A. Estes, S. Schaefer, and K. U. Malik Essential role of PKC-{zeta} in normal and angiotensin II-accelerated neointimal growth after vascular injury Am J Physiol Heart Circ Physiol, October 1, 2006; 291(4): H1602 - H1613. [Abstract] [Full Text] [PDF]

				M. Feletou and P. M. Vanhoutte Endothelial dysfunction: a multifaceted disorder (The Wiggers Award Lecture) Am J Physiol Heart Circ Physiol, September 1, 2006; 291(3): H985 - H1002. [Abstract] [Full Text] [PDF]

				Y. Chang, B. Ceacareanu, D. Zhuang, C. Zhang, Q. Pu, A. C. Ceacareanu, and A. Hassid Counter-Regulatory Function of Protein Tyrosine Phosphatase 1B in Platelet-Derived Growth Factor- or Fibroblast Growth Factor-Induced Motility and Proliferation of Cultured Smooth Muscle Cells and in Neointima Formation Arterioscler Thromb Vasc Biol, March 1, 2006; 26(3): 501 - 507. [Abstract] [Full Text] [PDF]

				F. Li, C. Zhang, S. Schaefer, A. Estes, and K. U. Malik ANG II-induced neointimal growth is mediated via cPLA2- and PLD2-activated Akt in balloon-injured rat carotid artery Am J Physiol Heart Circ Physiol, December 1, 2005; 289(6): H2592 - H2601. [Abstract] [Full Text] [PDF]

				C. Zhang, D. Chaturvedi, L. Jaggar, D. Magnuson, J. M. Lee, and T. B. Patel Regulation of Vascular Smooth Muscle Cell Proliferation and Migration by Human Sprouty 2 Arterioscler Thromb Vasc Biol, March 1, 2005; 25(3): 533 - 538. [Abstract] [Full Text] [PDF]

				Y. Chang, D. Zhuang, C. Zhang, and A. Hassid Increase of PTP levels in vascular injury and in cultured aortic smooth muscle cells treated with specific growth factors Am J Physiol Heart Circ Physiol, November 1, 2004; 287(5): H2201 - H2208. [Abstract] [Full Text] [PDF]