| Arginase promotes neointima formation in rat injured carotid arteries. | |
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MedLine Citation:
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PMID: 19164802 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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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:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2009-01-22 |
Journal Detail:
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Title: Arteriosclerosis, thrombosis, and vascular biology Volume: 29 ISSN: 1524-4636 ISO Abbreviation: Arterioscler. Thromb. Vasc. Biol. Publication Date: 2009 Apr |
Date Detail:
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Created Date: 2009-03-20 Completed Date: 2009-04-02 Revised Date: 2013-03-20 |
Medline Journal Info:
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Nlm Unique ID: 9505803 Medline TA: Arterioscler Thromb Vasc Biol Country: United States |
Other Details:
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Languages: eng Pagination: 488-94 Citation Subset: IM |
Affiliation:
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Department of Medical Pharmacology and Physiology, School of Medicine, University of Missouri-Columbia, Columbia, MO 65212, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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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:
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HL59976/HL/NHLBI NIH HHS; HL74966/HL/NHLBI NIH HHS; HL81720/HL/NHLBI NIH HHS; HL82774/HL/NHLBI NIH HHS; R01 HL059976-12/HL/NHLBI NIH HHS; R01 HL074966-04/HL/NHLBI NIH HHS; R01 HL081720/HL/NHLBI NIH HHS |
| Chemical | |
Reg. No./Substance:
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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; 74-79-3/Arginine; EC 3.5.3.1/Arginase |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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