Systems Network Genomic Analysis Reveals Cardioprotective Effect of MURC/Cavin-4 Deletion Against Ischemia/Reperfusion Injury.

Clicks: 478
ID: 47614
2019
Article Quality & Performance Metrics
Overall Quality
Not rated
Combines reader engagement with the AI quality analysis. This article has not been analysed, so there is no overall score — reader engagement is measured and shown alongside.
AI Quality Assessment
Not analyzed
Readership in this journal
Emerging

Ranked #5 of 266 articles by views in Journal of the American Heart Association

Most read Least read

Bar heights use a square-root scale. Only the 120 most-read articles are drawn; the journal has 266 in total.

Mint this article as an NFT
Not yet minted

Create a permanent, verifiable on-chain record of this article on the Scimatic Network. The NFT is held in your Journament account, and you can withdraw it to your own wallet at any time.

5 SUSD one-off · no wallet required
Sign in to mint
Abstract
Background Ischemia/reperfusion (I/R) injury is a critical issue in the development of treatment strategies for ischemic heart disease. MURC (muscle-restricted coiled-coil protein)/Cavin-4 (caveolae-associated protein 4), which is a component of caveolae, is involved in the pathophysiology of dilated cardiomyopathy and cardiac hypertrophy. However, the role of MURC in cardiac I/R injury remains unknown. Methods and Results The systems network genomic analysis based on PC-corr network inference on microarray data between wild-type and MURC knockout mouse hearts predicted a network of discriminating genes associated with reactive oxygen species. To demonstrate the prediction, we analyzed I/R-injured mouse hearts. MURC deletion decreased infarct size and preserved heart contraction with reactive oxygen species-related molecule EGR1 (early growth response protein 1) and DDIT4 (DNA-damage-inducible transcript 4) suppression in I/R-injured hearts. Because PC-corr network inference integrated with a protein-protein interaction network prediction also showed that MURC is involved in the apoptotic pathway, we confirmed the upregulation of STAT3 (signal transducer and activator of transcription 3) and BCL2 (B-cell lymphoma 2) and the inactivation of caspase 3 in I/R-injured hearts of MURC knockout mice compared with those of wild-type mice. STAT3 inhibitor canceled the cardioprotective effect of MURC deletion in I/R-injured hearts. In cardiomyocytes exposed to hydrogen peroxide, MURC overexpression promoted apoptosis and MURC knockdown inhibited apoptosis. STAT3 inhibitor canceled the antiapoptotic effect of MURC knockdown in cardiomyocytes. Conclusions Our findings, obtained by prediction from systems network genomic analysis followed by experimental validation, suggested that MURC modulates cardiac I/R injury through the regulation of reactive oxygen species-induced cell death and STAT3-meditated antiapoptosis. Functional inhibition of MURC may be effective in reducing cardiac I/R injury.
Reference Key
nishi2019systemsjournal Use this key to autocite in the manuscript while using SciMatic Manuscript Manager or Thesis Manager
Authors Nishi, Masahiro;Ogata, Takehiro;Cannistraci, Carlo Vittorio;Ciucci, Sara;Nakanishi, Naohiko;Higuchi, Yusuke;Sakamoto, Akira;Tsuji, Yumika;Mizushima, Katsura;Matoba, Satoaki;
Journal Journal of the American Heart Association
Year 2019
DOI
10.1161/JAHA.119.012047
URL
Keywords
systems biology apoptosis ischemia reperfusion injury reactive oxygen species caveolae

Citations

No citations found. To add a citation, contact the admin at info@scimatic.org

Comments

No comments yet. Be the first to comment on this article.