| Overexpression of CD39/nucleoside triphosphate diphosphohydrolase-1 decreases smooth muscle cell proliferation and prevents neointima formation after angioplasty. | |
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MedLine Citation:
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PMID: 18485080 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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BACKGROUND: Growing evidence implicates the involvement of extracellular nucleotides in the regulation of platelet, leukocyte, endothelial cell (EC) and vascular smooth muscle cell (VSMC) phenotype and function. Within the quiescent vasculature, extracellular nucleotides are rapidly hydrolyzed by CD39, the dominant endothelial nucleoside triphosphate diphosphohydrolase (NTPDase-1). However, vascular CD39/NTPDase-1 activity is lost in EC activated by oxidative stress or proinflammatory mediators, and upon denudation of the endothelium following balloon injury. The consequent increase in extracellular nucleotide concentrations triggers signaling events leading to prothrombotic responses and increased VSMC proliferation. OBJECTIVES: To investigate the effect of overexpressed CD39/NTPDase-1 in injured aorta. Methods: Using adenoviral-mediated gene transfer we expressed CD39/NTPDase-1 in mechanically denudated rat aortas. We measured intima formation by morphometry and VSMC proliferation by the [(3)H]-thymidine incorporation assay. RESULTS: Targeted expression of CD39 in injured vessels increased NTPDase activity (from 2.91 +/- 0.31 to 22.07 +/- 6.7 nmols Pi mg(-1) protein, 4 days after exposure to the adenovirus) and prevented the formation of neointima. The thickness of the intimal layer in injured aortas exposed to Ad-CD39 was 26.2 +/- 3.9 microm vs. 51.8 +/- 6.1 microm and 64.4 +/- 22.2 microm (P < 0.001) in vessels treated with Ad-beta-gal and saline, respectively. Moreover, targeted expression of CD39/NTPDase-1 caused a 70% (P < 0.01) decrease in proliferation of VSMC isolated from transduced rat aortas as compared with VSMC derived from control vessels. CONCLUSIONS: The presented data suggest that increasing CD39/NTPDase-1 activity in VSMC could represent a novel therapeutic approach for the prevention of stenosis associated with angioplasty and other occlusive vascular diseases. |
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Authors:
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K Koziak; M Bojakowska; S C Robson; K Bojakowski; J Soin; E Csizmadia; P Religa; Z Gaciong; E Kaczmarek |
Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural Date: 2008-07-01 |
Journal Detail:
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Title: Journal of thrombosis and haemostasis : JTH Volume: 6 ISSN: 1538-7836 ISO Abbreviation: J. Thromb. Haemost. Publication Date: 2008 Jul |
Date Detail:
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Created Date: 2008-07-08 Completed Date: 2008-08-13 Revised Date: 2013-02-11 |
Medline Journal Info:
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Nlm Unique ID: 101170508 Medline TA: J Thromb Haemost Country: England |
Other Details:
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Languages: eng Pagination: 1191-7 Citation Subset: IM |
Affiliation:
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Department of General and Nutritional Biochemistry, The Medical University of Warsaw, Warsaw, Poland. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Angioplasty
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adverse effects* Animals Antigens, CD / genetics, physiology* Apyrase / genetics, physiology* Cell Proliferation* Gene Expression Regulation Humans Male Mice Mice, Transgenic Muscle, Smooth, Vascular / cytology Myocytes, Smooth Muscle / cytology* Rats Rats, Inbred F344 Tunica Intima / cytology* |
| Grant Support | |
ID/Acronym/Agency:
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HL57307/HL/NHLBI NIH HHS; HL63972/HL/NHLBI NIH HHS; HL66167/HL/NHLBI NIH HHS; R01 HL057307/HL/NHLBI NIH HHS; R01 HL057307-08/HL/NHLBI NIH HHS; R01 HL066167-04/HL/NHLBI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Antigens, CD; EC 3.6.1.5/Apyrase; EC 3.6.1.5/CD39 antigen |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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