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

Journal of the American Heart Association
Masahiro NishiSatoaki Matoba

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 ina...Continue Reading

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Citations

Nov 28, 2019·American Journal of Physiology. Heart and Circulatory Physiology·Wei ZhangJie Chao
Dec 3, 2021·ESC Heart Failure·Masahiro NishiSatoaki Matoba

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Datasets Mentioned

BETA
GSE125308

Methods Mentioned

BETA
PCA
interaction prediction
ELISA
transfection
Assay
PCR
protein knockout
immunoprecipitation

Software Mentioned

R Foundation for Statistical Computing
corr
PC
PPIN
MATLAB
Cytoscape
R
ImageJ
DAVID
ZEN

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