Differential gene expression in infarct scar and viable myocardium from rat heart following coronary ligation.
Post-myocardial infarction (MI) remodeling of cardiac myocytes and the myocardial interstitium results in alteration of gross ventricular geometry and ventricular dysfunction. To investigate the mechanisms of the remodeling process of the heart after large MI, the expression of various genes in viable left ventricle and infarct scar tissue were examined at 16 weeks post-MI. Steady-state expression of Na(+)-K+ ATPase alpha-1 and -2, phospholamban (PLB), alpha-myosin heavy chain (alpha-MHC), ryanodine receptor (Rya) and Ca2+ ATPase (Serca2) mRNAs were decreased in the infarct scar vs noninfarcted sham-operated controls (P < 0.05). On the other hand, Gialpha2 and beta-MHC mRNAs were upregulated (P < 0.05, respectively) in the infarct scar whereas Na(+)-K+ ATPase-beta, Na(+)-Ca2+ exchanger and Gs mRNAs were not altered vs control values. In viable left ventricle, the alpha-1 subunit of Na(+)-K+ ATPase, alpha-3, beta-isoforms, Rya, beta-MHC, Gialpha2, Gs and Na(+)-Ca2+ exchanger were significantly elevated while expression of the alpha-2 subunit of Na(+)-K+ ATPase, PLB and Serca2 were significantly decreased compared to controls. Expression of CK2alpha mRNA was elevated in noninfarcted heart (145 +/- 15%) and diminished in the infarct scar (66 +/- 13%) vs controls. Expression of beta-MHC mRNA was elevated in both viable and infarct scar tissues of experimental hearts (140 +/- 31% and 183 +/- 30% vs. controls, respectively). These results suggest that cardiac genes in the infarcted tissue and viable left ventricle following MI are differentially regulated.
Xu
Y-J
YJ
Institute of Cardiovascular Sciences, St. Boniface General Hospital Research Centre and Department of Physiology, Faculty of Medicine University of Manitoba, Winnipeg, Canada.
Chapman
D
D
Dixon
I M C
IM
Sethi
R
R
Guo
X
X
Dhalla
N S
NS
D000818:Animals; D015152:Blotting, Northern; D047390:Casein Kinase II; D002921:Cicatrix / Q000473:pathology*; D018076:DNA, Complementary / Q000378:metabolism; D019204:GTP-Binding Proteins / Q000378:metabolism; D005786:Gene Expression Regulation; D006352:Heart Ventricles / Q000473:pathology*; D006801:Humans; D017379:Hypertrophy, Left Ventricular; D008297:Male; D009203:Myocardial Infarction / Q000473:pathology* / Q000601:surgery*; D009206:Myocardium / Q000378:metabolism / Q000473:pathology*; D018995:Myosin Heavy Chains / Q000096:biosynthesis; D020411:Oligonucleotide Array Sequence Analysis; D017346:Protein Serine-Threonine Kinases / Q000096:biosynthesis; D012313:RNA / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D019831:Sodium-Calcium Exchanger / Q000378:metabolism; D000254:Sodium-Potassium-Exchanging ATPase / Q000096:biosynthesis; D015854:Up-Regulation
D018076:DNA, Complementary; D012333:RNA, Messenger; D019831:Sodium-Calcium Exchanger; D012313:RNA; D047390:Casein Kinase II; D017346:Protein Serine-Threonine Kinases; D019204:GTP-Binding Proteins; D018995:Myosin Heavy Chains; D000254:Sodium-Potassium-Exchanging ATPase