Glutaredoxin-1 overexpression enhances neovascularization and diminishes ventricular remodeling in chronic myocardial infarction

Ram Sudheer Adluri, Mahesh Thirunavukkarasu, Lijun Zhan, Nageswara Rao Dunna, Yuzo Akita, Vaithinathan Selvaraju, Hajime Otani, Juan Sanchez, Ye Shih Ho, Nilanjana Maulik

Research output: Contribution to journalArticle

Abstract

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-1Tg/+) mice were randomized into wild-type sham (WTS), Grx-1Tg/+ Sham (Grx-1Tg/+S), WTMI, Grx-1Tg/+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-1Tg/+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-1Tg/+MI group as compared to the WTMI animals. Moreover, attenuation of oxidative stress and apoptotic cardiomyocytes was observed in the Grx-1Tg/+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-1Tg/+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.

Original languageEnglish (US)
Article numbere34790
JournalPLoS One
Volume7
Issue number4
DOIs
StatePublished - Apr 16 2012
Externally publishedYes

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Glutaredoxins
Ventricular Remodeling
myocardial infarction
angiogenesis
Myocardial Infarction
Animals
Thioredoxins
Oxidative stress
animals
oxidative stress
Vascular Endothelial Growth Factor A
Oxidation-Reduction
Oxidative Stress
coronary vessels
heart failure
myocardium
pathophysiology
thiols
shortenings
Scavenging

ASJC Scopus subject areas

  • Medicine(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Adluri, R. S., Thirunavukkarasu, M., Zhan, L., Dunna, N. R., Akita, Y., Selvaraju, V., ... Maulik, N. (2012). Glutaredoxin-1 overexpression enhances neovascularization and diminishes ventricular remodeling in chronic myocardial infarction. PLoS One, 7(4), [e34790]. https://doi.org/10.1371/journal.pone.0034790

Glutaredoxin-1 overexpression enhances neovascularization and diminishes ventricular remodeling in chronic myocardial infarction. / Adluri, Ram Sudheer; Thirunavukkarasu, Mahesh; Zhan, Lijun; Dunna, Nageswara Rao; Akita, Yuzo; Selvaraju, Vaithinathan; Otani, Hajime; Sanchez, Juan; Ho, Ye Shih; Maulik, Nilanjana.

In: PLoS One, Vol. 7, No. 4, e34790, 16.04.2012.

Research output: Contribution to journalArticle

Adluri, RS, Thirunavukkarasu, M, Zhan, L, Dunna, NR, Akita, Y, Selvaraju, V, Otani, H, Sanchez, J, Ho, YS & Maulik, N 2012, 'Glutaredoxin-1 overexpression enhances neovascularization and diminishes ventricular remodeling in chronic myocardial infarction', PLoS One, vol. 7, no. 4, e34790. https://doi.org/10.1371/journal.pone.0034790
Adluri, Ram Sudheer ; Thirunavukkarasu, Mahesh ; Zhan, Lijun ; Dunna, Nageswara Rao ; Akita, Yuzo ; Selvaraju, Vaithinathan ; Otani, Hajime ; Sanchez, Juan ; Ho, Ye Shih ; Maulik, Nilanjana. / Glutaredoxin-1 overexpression enhances neovascularization and diminishes ventricular remodeling in chronic myocardial infarction. In: PLoS One. 2012 ; Vol. 7, No. 4.
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