Over-expression of calpastatin inhibits calpain activation and attenuates post-infarction myocardial remodeling

PloS One
Tingqiao YeShuangtao Ma

Abstract

Calpain is activated following myocardial infarction and ablation of calpastatin (CAST), an endogenous inhibitor of calpains, promotes left ventricular remodeling after myocardial infarction (MI). The present study aimed to investigate the effect of transgenic over-expression of CAST on the post-infarction myocardial remodeling process. We established transgenic mice (TG) ubiquitously over-expressing human CAST protein and produced MI in TG mice and C57BL/6J wild-type (WT) littermates. The CAST protein expression was profoundly upregulated in the myocardial tissue of TG mice compared with WT littermates (P < 0.01). Overexpression of CAST significantly reduced the infarct size (P < 0.01) and blunted MI-induced interventricular hypertrophy, global myocardial fibrosis and collagen I and collagen III deposition, hypotension and hemodynamic disturbances at 21 days after MI. Moreover, the MI-induced up-regulation and activation of calpains were obviously attenuated in CAST TG mice. MI-induced down-regulation of CAST was partially reversed in TG mice. Additionally, the MI-caused imbalance of matrix metalloproteinases and their inhibitors was improved in TG mice. Transgenic over-expression of CAST inhibits calpain activation and attenu...Continue Reading

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Citations

May 2, 2017·Cardiovascular Research·Marcos PoncelasDavid Garcia-Dorado
Oct 23, 2019·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Aminah A LoonatJames E Clark
Mar 21, 2020·Journal of Cardiovascular Pharmacology·Ken ChenDachun Yang
Mar 28, 2019·Basic Research in Cardiology·David AlujaDavid Garcia-Dorado
Oct 11, 2015·American Journal of Physiology. Heart and Circulatory Physiology·Feng WanBarnabas Gellen
Oct 4, 2020·Critical Care Medicine·Haikel DridiSamir Jaber
Sep 4, 2018·JACC. Basic to Translational Science·Yihui WangLong-Sheng Song

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Methods Mentioned

BETA
transgenic
Protein Assay
PCR
Genotyping

Software Mentioned

SPSS

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