title: Expression of Gi-2 alpha and Gs alpha in myofibroblasts localized to the infarct scar in heart failure due to myocardial infarction.
abstract: OBJECTIVE
  Patients surviving large transmural myocardial infarction (MI) are at risk for congestive heart failure with attendant alteration of ventricular geometry and scar remodeling. Altered Gi-2 alpha and Gs alpha protein expression may be involved in cardiac remodeling associated with heart failure, however their expression in scar tissue remains unclear.
  
  
  METHODS
  MI was produced in Sprague-Dawley rats by ligation of the left coronary artery. Gi-2 alpha and Gs alpha protein concentration, localization and mRNA abundance were noted in surviving left ventricle remote to the infarct, in border and in scar tissues from 8 week post-MI hearts with moderate heart failure.
  
  
  RESULTS
  We observed a 4.5- and 5.0-fold increase in immunoreactive Gi-2 alpha protein concentration occurs in the border and scar regions vs. control values, respectively, in 8-week post-MI rat hearts. Similarly, immunoreactive Gs alpha protein concentration was increased 3.4- and 8.2-fold, respectively, in these tissues vs. controls. Double-fluorescence labeling and phenotyping studies revealed that both Gi-2 alpha and Gs alpha proteins were localized to myofibroblasts in the infarct scar and to viable myocytes bordering the scar. Northern analysis revealed that the Gi-2 alpha/GAPDH ratio was increased in both viable and scar regions (1.24- and 1.85-fold respectively) from experimental hearts when compared to sham-operated control values when compared to noninfarcted left ventricle, the value of this ratio in scar tissue was elevated approximately 1.5 fold. The Gs alpha/GAPDH ratio was significantly increased (1.28-fold) only in the scar region vs. control.
  
  
  CONCLUSIONS
  Our results indicate a marked increase in the expression of Gi-2 alpha and Gs alpha from myofibroblasts of the infarct scar as well as remnant myocytes bordering the scar in 8-week post-MI rat hearts. We suggest that these changes may be associated with ongoing remodeling in the infarct scar in chronic post-MI phase of this experimental model.
authors.affiliation: Molecular Cardiology Laboratory, St. Boniface General Hospital Research Centre, Faculty of Medicine, University of Manitoba, Winnipeg, Canada.
authors.forename: D J
authors.initials: DJ
authors.lastname: Peterson
authors.forename: H
authors.initials: H
authors.lastname: Ju
authors.forename: J
authors.initials: J
authors.lastname: Hao
authors.forename: M
authors.initials: M
authors.lastname: Panagia
authors.forename: D C
authors.initials: DC
authors.lastname: Chapman
authors.forename: I M
authors.initials: IM
authors.lastname: Dixon
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D015152:Blotting, Northern; D015153:Blotting, Western; D005347:Fibroblasts / Q000378:metabolism / Q000473:pathology; D005455:Fluorescent Antibody Technique; D019206:GTP-Binding Protein alpha Subunits, Gi-Go / Q000032:analysis / Q000235:genetics / Q000378:metabolism; D019205:GTP-Binding Protein alpha Subunits, Gs / Q000032:analysis / Q000235:genetics / Q000378:metabolism; D019204:GTP-Binding Proteins / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D015870:Gene Expression; D006333:Heart Failure / Q000378:metabolism* / Q000473:pathology; D008297:Male; D009203:Myocardial Infarction / Q000378:metabolism* / Q000473:pathology; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D012333:RNA, Messenger; D019204:GTP-Binding Proteins; D019206:GTP-Binding Protein alpha Subunits, Gi-Go; D019205:GTP-Binding Protein alpha Subunits, Gs