Document Detail


Glutaredoxin-1 overexpression enhances neovascularization and diminishes ventricular remodeling in chronic myocardial infarction.
MedLine Citation:
PMID:  22523530     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Oxidative stress plays a critical role in the pathophysiology of cardiac failure, including the modulation of neovascularization following myocardial infarction (MI). Redox molecules thioredoxin (Trx) and glutaredoxin (Grx) superfamilies actively maintain intracellular thiol-redox homeostasis by scavenging reactive oxygen species. Among these two superfamilies, the pro-angiogenic function of Trx-1 has been reported in chronic MI model whereas similar role of Grx-1 remains uncertain. The present study attempts to establish the role of Grx-1 in neovascularization and ventricular remodeling following MI. Wild-type (WT) and Grx-1 transgenic (Grx-1(Tg/+)) mice were randomized into wild-type sham (WTS), Grx-1(Tg/+) Sham (Grx-1(Tg/+)S), WTMI, Grx-1(Tg/+)MI. MI was induced by permanent occlusion of the LAD coronary artery. Sham groups underwent identical time-matched surgical procedures without LAD ligation. Significant increase in arteriolar density was observed 7 days (d) after surgical intervention in the Grx-1(Tg/+)MI group as compared to the WTMI animals. Further, improvement in myocardial functional parameters 30 d after MI was observed including decreased LVIDs, LVIDd, increased ejection fraction and, fractional shortening was also observed in the Grx-1(Tg/+)MI group as compared to the WTMI animals. Moreover, attenuation of oxidative stress and apoptotic cardiomyocytes was observed in the Grx-1(Tg/+)MI group as compared to the WTMI animals. Increased expression of p-Akt, VEGF, Ang-1, Bcl-2, survivin and DNA binding activity of NF-κB were observed in the Grx-1(Tg/+)MI group when compared to WTMI animals as revealed by Western blot analysis and Gel-shift analysis, respectively. These results are the first to demonstrate that Grx-1 induces angiogenesis and diminishes ventricular remodeling apparently through neovascularization mediated by Akt, VEGF, Ang-1 and NF-κB as well as Bcl-2 and survivin-mediated anti-apoptotic pathway in the infarcted myocardium.
Authors:
Ram Sudheer Adluri; Mahesh Thirunavukkarasu; Lijun Zhan; Nageswara Rao Dunna; Yuzo Akita; Vaithinathan Selvaraju; Hajime Otani; Juan A Sanchez; Ye-Shih Ho; Nilanjana Maulik
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2012-04-16
Journal Detail:
Title:  PloS one     Volume:  7     ISSN:  1932-6203     ISO Abbreviation:  PLoS ONE     Publication Date:  2012  
Date Detail:
Created Date:  2012-04-23     Completed Date:  2012-07-18     Revised Date:  2013-06-26    
Medline Journal Info:
Nlm Unique ID:  101285081     Medline TA:  PLoS One     Country:  United States    
Other Details:
Languages:  eng     Pagination:  e34790     Citation Subset:  IM    
Copyright Information:
© 2012 Adluri et al.
Affiliation:
Molecular Cardiology and Angiogenesis Laboratory, Department of Surgery, Health Center, University of Connecticut, Farmington, Connecticut, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Apoptosis
Base Sequence
Chronic Disease
Glutaredoxins / metabolism*
Male
Mice
Mice, Transgenic
Myocardial Infarction / enzymology,  metabolism,  pathology*
Myocardium / metabolism,  pathology
NF-kappa B / metabolism
Neovascularization, Pathologic*
Oligonucleotides
Phosphorylation
Proto-Oncogene Proteins c-akt / metabolism
Reactive Oxygen Species / metabolism
Ventricular Remodeling*
bcl-2-Associated X Protein / metabolism
Grant Support
ID/Acronym/Agency:
HL-69910/HL/NHLBI NIH HHS; HL-85804/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Glutaredoxins; 0/NF-kappa B; 0/Oligonucleotides; 0/Reactive Oxygen Species; 0/bcl-2-Associated X Protein; EC 2.7.11.1/Proto-Oncogene Proteins c-akt
Comments/Corrections

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