title: Over-expression of calpastatin inhibits calpain activation and attenuates post-infarction myocardial remodeling.
abstract: BACKGROUND
  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.
  
  
  METHODS
  We established transgenic mice (TG) ubiquitously over-expressing human CAST protein and produced MI in TG mice and C57BL/6J wild-type (WT) littermates.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  Transgenic over-expression of CAST inhibits calpain activation and attenuates post-infarction myocardial remodeling.
authors.affiliation: Department of Cardiology, Chengdu Military General Hospital, Chengdu, Sichuan, China.
authors.forename: Tingqiao
authors.initials: T
authors.lastname: Ye
authors.affiliation: Department of Cardiology, Chengdu Military General Hospital, Chengdu, Sichuan, China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Department of Cardiology, Chengdu Military General Hospital, Chengdu, Sichuan, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Cardiology, Chengdu Military General Hospital, Chengdu, Sichuan, China.
authors.forename: Xiaofeng
authors.initials: X
authors.lastname: Song
authors.affiliation: Department of Cardiology, Chengdu Military General Hospital, Chengdu, Sichuan, China.
authors.forename: Dachun
authors.initials: D
authors.lastname: Yang
authors.affiliation: Department of Cardiology, Chengdu Military General Hospital, Chengdu, Sichuan, China.
authors.forename: De
authors.initials: D
authors.lastname: Li
authors.affiliation: Department of Cardiology, Chengdu Military General Hospital, Chengdu, Sichuan, China.
authors.forename: Dan
authors.initials: D
authors.lastname: Li
authors.affiliation: Department of Cardiology, Chengdu Military General Hospital, Chengdu, Sichuan, China.
authors.forename: Linan
authors.initials: L
authors.lastname: Su
authors.affiliation: Department of Cardiology, Chengdu Military General Hospital, Chengdu, Sichuan, China.
authors.forename: Yongjian
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Department of Cardiology, Chengdu Military General Hospital, Chengdu, Sichuan, China.
authors.forename: Shuangtao
authors.initials: S
authors.lastname: Ma
mesh_terms: D000818:Animals; D002154:Calpain / Q000235:genetics* / Q000378:metabolism; D006332:Cardiomegaly / Q000201:enzymology / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D024042:Collagen Type I / Q000235:genetics / Q000378:metabolism; D024061:Collagen Type III / Q000235:genetics / Q000378:metabolism; D003598:Cytoskeletal Proteins / Q000235:genetics* / Q000378:metabolism; D004195:Disease Models, Animal; D004789:Enzyme Activation; D005260:Female; D005355:Fibrosis; D005786:Gene Expression Regulation; D006801:Humans; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism; D008297:Male; D061965:Matrix Metalloproteinase Inhibitors / Q000378:metabolism; D053505:Matrix Metalloproteinases, Secreted / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009203:Myocardial Infarction / Q000201:enzymology / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D016019:Survival Analysis; D016277:Ventricular Function, Left / Q000235:genetics*; D020257:Ventricular Remodeling / Q000235:genetics*
chemical_list: D024042:Collagen Type I; D024061:Collagen Type III; D003598:Cytoskeletal Proteins; C505599:Erc2 protein, mouse; D007527:Isoenzymes; D061965:Matrix Metalloproteinase Inhibitors; D002154:Calpain; D053505:Matrix Metalloproteinases, Secreted