Document Detail


Arginase promotes neointima formation in rat injured carotid arteries.
MedLine Citation:
PMID:  19164802     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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 investigated the impact of arginase on cell cycle progression and neointima formation after experimental arterial injury.
METHODS AND RESULTS: Balloon injury of rat carotid arteries resulted in a sustained increase in arginase activity in the vessel wall and the induction of arginase I protein in both the media and neointima of injured vessels. Furthermore, local perivascular application of the potent and selective arginase inhibitors S-(2-boronoethyl)-L-cysteine (BEC) or N(G)-hydroxy-nor-L-arginine (L-OHNA) immediately after injury markedly attenuated medial and neointimal DNA synthesis and neointima formation. Substantial arginase I protein and arginase activity was also detected in rat cultured aortic VSMCs. Moreover, treatment of VSMCs with BEC or L-OHNA, or knockdown of arginase I protein, arrested cells in the G(0)/G(1) phase of the cell cycle and induced the expression of the cyclin-dependent protein kinase inhibitor, p21.
CONCLUSIONS: This study demonstrates that arginase is essential for VSMCs to enter the cell cycle and that arginase I contributes to the remodeling response after arterial injury. Arginase I represents a potentially new therapeutic target for the treatment of vasculoproliferative disorders.
Authors:
Kelly J Peyton; Diana Ensenat; Mohammed A Azam; Amit N Keswani; Sankaranarayanan Kannan; Xiao-ming Liu; Hong Wang; David A Tulis; William Durante
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2009-01-22
Journal Detail:
Title:  Arteriosclerosis, thrombosis, and vascular biology     Volume:  29     ISSN:  1524-4636     ISO Abbreviation:  Arterioscler. Thromb. Vasc. Biol.     Publication Date:  2009 Apr 
Date Detail:
Created Date:  2009-03-20     Completed Date:  2009-04-02     Revised Date:  2014-09-18    
Medline Journal Info:
Nlm Unique ID:  9505803     Medline TA:  Arterioscler Thromb Vasc Biol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  488-94     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Animals
Arginase / antagonists & inhibitors,  genetics,  metabolism*
Arginine / analogs & derivatives,  pharmacology
Boronic Acids / pharmacology
Carotid Artery Injuries / enzymology*,  pathology
Cell Cycle
Cell Proliferation
Cells, Cultured
Cyclin-Dependent Kinase Inhibitor p21 / metabolism
Disease Models, Animal
Hyperplasia
Male
Muscle, Smooth, Vascular / drug effects,  enzymology*,  injuries,  pathology
Myocytes, Smooth Muscle / drug effects,  enzymology*,  pathology
RNA Interference
RNA, Small Interfering / metabolism
Rats
Rats, Sprague-Dawley
Time Factors
Tunica Intima / drug effects,  enzymology*,  injuries,  pathology
Up-Regulation
Grant Support
ID/Acronym/Agency:
HL59976/HL/NHLBI NIH HHS; HL74966/HL/NHLBI NIH HHS; HL81720/HL/NHLBI NIH HHS; HL82774/HL/NHLBI NIH HHS; R01 HL059976/HL/NHLBI NIH HHS; R01 HL074966/HL/NHLBI NIH HHS; R01 HL074966-04/HL/NHLBI NIH HHS; R01 HL081720/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/(2-boronoethyl)-cysteine; 0/Boronic Acids; 0/Cdkn1a protein, rat; 0/Cyclin-Dependent Kinase Inhibitor p21; 0/N(omega)-hydroxynorarginine; 0/RNA, Small Interfering; 94ZLA3W45F/Arginine; EC 3.5.3.1/Arginase
Comments/Corrections

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