| 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: 2013-05-20 |
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. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| 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 | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: ENCODING AND DECODING V1 FMRI RESPONSES TO NATURAL IMAGES WITH SPARSE NONPARAMETRIC MODELS.
Next Document: Correction: Sensory coding by cerebellar mossy fibres through inhibition-driven phase resetting and ...