Document Detail


Hyperoxia and transforming growth factor β1 signaling in the post-ischemic mouse heart.
MedLine Citation:
PMID:  23352974     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
AIMS: Following ischemic injury, myocardial healing and remodeling occur with characteristic myofibroblast trans-differentiation and scar formation. The current study tests the hypothesis that hyperoxia and nitric oxide (NO) regulate TGF-β1 signaling in the post-ischemic myocardium.
MAIN METHODS: C57BL/6 wild-type (WT), endothelial and inducible nitric oxide synthase knockout (eNOS(-/-) and iNOS(-/-)) mice were subjected to 30-min left anterior descending coronary artery occlusion followed by reperfusion. Myocardial tissue oxygenation was monitored with electron paramagnetic resonance oximetry. Protein expressions of TGF-β1, receptor-activated small mothers against decapentaplegic homolog (Smad), p21 and α-smooth muscle actin (α-SMA) were measured with enzyme-linked immunosorbent assay (ELISA), Western immunoblotting, and immunohistochemical staining.
KEY FINDINGS: There was a hyperoxic state in the post-ischemic myocardial tissue. Protein expressions of total and active TGF-β1, p-Smad2/3 over t-Smad2/3 ratio, p21, and α-SMA were significantly increased in WT mice compared to Sham control. Knockout of eNOS or iNOS further increased protein expression of these signals. The expression of α-SMA was more abundant in the infarct of eNOS(-/-) and iNOS(-/-) mice than WT mice. A protein band indicating nitration of TGF-β type-II receptor (TGFβRII) was observed from WT heart. Carbogen (95% O2 plus 5% CO2) treatment increased the ratio of p-Smad2/t-Smad2, which was inhibited by 10006329 EUK (EUK134) and sodium nitroprusside (SNP). In conclusion, hyperoxia up-regulated and NO/ONOO(-) inhibited cardiac TGF-β1 signaling and myofibroblast trans-differentiation.
SIGNIFICANCE: These findings may provide new insights in myocardial infarct healing and repair.
Authors:
Yuanjing Li; Ming Cai; Qinghua Sun; Zhenguo Liu; Arturo J Cardounel; Harold M Swartz; Guanglong He
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2013-01-24
Journal Detail:
Title:  Life sciences     Volume:  92     ISSN:  1879-0631     ISO Abbreviation:  Life Sci.     Publication Date:  2013 Mar 
Date Detail:
Created Date:  2013-03-04     Completed Date:  2013-04-23     Revised Date:  2013-06-13    
Medline Journal Info:
Nlm Unique ID:  0375521     Medline TA:  Life Sci     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  547-54     Citation Subset:  IM    
Copyright Information:
Copyright © 2013 Elsevier Inc. All rights reserved.
Affiliation:
Davis Heart and Lung Research Institute and Division of Cardiovascular Medicine, Department of Internal Medicine, The Ohio State University Wexner Medical Center, Columbus, OH 43210, USA.
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MeSH Terms
Descriptor/Qualifier:
Actins / metabolism
Animals
Blotting, Western
Cell Differentiation / drug effects
Electron Spin Resonance Spectroscopy
Enzyme-Linked Immunosorbent Assay
Hyperoxia / etiology,  metabolism*
Immunohistochemistry
Mice
Mice, Inbred C57BL
Mice, Knockout
Myocardial Ischemia / complications*
Myofibroblasts / cytology
Nitric Oxide / metabolism*
Nitric Oxide Synthase Type II / genetics
Nitric Oxide Synthase Type III / genetics
Oximetry
Signal Transduction / physiology*
Smad2 Protein / metabolism
Smad3 Protein / metabolism
Transforming Growth Factor beta1 / metabolism*
Grant Support
ID/Acronym/Agency:
ES016588/ES/NIEHS NIH HHS; ES018900/ES/NIEHS NIH HHS; HL081630/HL/NHLBI NIH HHS; HL081734/HL/NHLBI NIH HHS; HL094650/HL/NHLBI NIH HHS; K01 ES016588/ES/NIEHS NIH HHS; P01 EB002180/EB/NIBIB NIH HHS; P01 EB2180/EB/NIBIB NIH HHS; R01 ES018900/ES/NIEHS NIH HHS; R01 HL081630/HL/NHLBI NIH HHS; R01 HL081734/HL/NHLBI NIH HHS; R01 HL094650/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Acta2 protein, mouse; 0/Actins; 0/Smad2 Protein; 0/Smad2 protein, mouse; 0/Smad3 Protein; 0/Smad3 protein, mouse; 0/Transforming Growth Factor beta1; 10102-43-9/Nitric Oxide; EC 1.14.13.39/Nitric Oxide Synthase Type II; EC 1.14.13.39/Nitric Oxide Synthase Type III; EC 1.14.13.39/Nos2 protein, mouse; EC 1.14.13.39/Nos3 protein, mouse

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