Arginase Promotes Neointima Formation in Rat Injured Carotid Arteries

ECU Author/Contributor (non-ECU co-authors, if there are any, appear on document)

Mohammed A. Azam (Creator)

William Durante (Creator)

Diana Ensenat (Creator)

Sankaranarayanan Kannan (Creator)

Amit N. Keswani (Creator)

Xiao-ming Liu (Creator)

Kelly J. Peyton (Creator)

David A. Tulis (Creator)

Hong Wang (Creator)

Institution

East Carolina University (ECU )

Web Site: http://www.ecu.edu/lib/

Abstract: Objective—Arginase stimulates the proliferation of cultured vascular smooth muscle cells VSMCs); however the influence of arginase on VSMC growth in vivo is not known. This study nvestigated the impact of arginase on cell cycle progression and neointima formation following xperimental arterial injury. ethods and Results—Balloon injury of rat carotid arteries resulted in a sustained increase in rginase activity in the vessel wall and the induction of arginase I protein in both the media and eointima of injured vessels. Furthermore local perivascular application of the potent and selective rginase inhibitors S-(2-boronoethyl)-L-cysteine (BEC) or NG-hydroxy-nor-L-arginine (L-OHNA) mmediately after injury markedly attenuated medial and neointimal DNA synthesis and neointima ormation. Substantial arginase I protein and arginase activity was also detected in rat cultured aortic SMCs. Moreover treatment of VSMCs with BEC or L-OHNA or knockdown of arginase I protein rrested cells in the G0/G1 phase of the cell cycle and induced the expression of the cyclin-dependent rotein kinase inhibitor p21. onclusion—This study demonstrates that arginase is essential for VSMCs to enter the cell cycle nd that arginase I contributes to the remodeling response following arterial injury. Arginase I epresents a potentially new therapeutic target for the treatment of vasculoproliferative disorders.Originally published Arteriosclerosis Thrombosis and Vascular Biology Vol. 29 No. 4 Apr 2009

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Publication

Other

Arteriosclerosis Thrombosis and Vascular Biology. 29:4(April 2009) p. 488-494.

Language: English

Date: 2011

Keywords

arginase, vascular smooth muscle cell poliferation, neointima

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