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

• Published in: PloS one Vol. 10; no. 3; p. e0120178
• Main Authors: Ye, Tingqiao, Wang, Qiang, Zhang, Yan, Song, Xiaofeng, Yang, Dachun, Li, De, Li, Dan, Su, Linan, Yang, Yongjian, Ma, Shuangtao
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 18.03.2015; Public Library of Science (PLoS)
• Subjects: Ablation (Surgery); Activation; Animals; Attenuation; Calpain; Calpain - genetics; Calpain - metabolism; Calpastatin; Cardiology; Cardiomegaly - enzymology; Cardiomegaly - genetics; Cardiomegaly - mortality; Cardiomegaly - pathology; Cholesterol; Collagen; Collagen (type I); Collagen (type III); Collagen Type I - genetics; Collagen Type I - metabolism; Collagen Type III - genetics; Collagen Type III - metabolism; Comparative analysis; Cytoskeletal Proteins - genetics; Cytoskeletal Proteins - metabolism; Diabetes; Disease Models, Animal; Enzyme Activation; Female; Fibrosis; Gene Expression Regulation; Genetic engineering; Heart; Heart attack; Heart attacks; Heart failure; House mouse; Humans; Hypertrophy; Hypotension; Isoenzymes - genetics; Isoenzymes - metabolism; Laboratory animals; Male; Matrix Metalloproteinase Inhibitors - metabolism; Matrix metalloproteinases; Matrix Metalloproteinases, Secreted - genetics; Matrix Metalloproteinases, Secreted - metabolism; Mice; Mice, Inbred C57BL; Mice, Transgenic; Myocardial infarction; Myocardial Infarction - enzymology; Myocardial Infarction - genetics; Myocardial Infarction - mortality; Myocardial Infarction - pathology; Ostomy; Overexpression; Proteins; Rodents; Survival Analysis; Transgenic animals; Transgenic mice; Ventricle; Ventricular Function, Left - genetics; Ventricular Remodeling - genetics; United States > US; China
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0120178

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 attenuates post-infarction myocardial remodeling.