Molecular mechanism of hypertrophied failing heart--abnormalities of the diastolic properties and contractility.
The clinical syndrome of heart failure occurs as a consequence of the limitation of compensatory mechanisms, such as cardiac hypertrophy. To clarify transcriptional changes in specific genes in failing hearts, we examined the expression of cardiac Ca(2+)+Mg(2+)-dependent ATPase in the sarcoplasmic reticulum and transforming growth factor beta genes in the ventricles of rat hypertrophied heart, and the expression of guanine nucleotide-binding protein and "fetal" contractile protein genes in the ventricles of cardiomyopathic Syrian hamsters of Bio14.6. Northern blot analysis of total cellular RNA revealed that the mRNA levels of Ca(2+)+Mg(2+)-dependent ATPase were decreased by pressure overload and became 32% of sham in 1 month, and were correlated with corresponding protein levels. Transforming growth factor beta mRNA, a potent activator of collagen synthesis, was increased by pressure overload. The expression levels of the Gs alpha mRNA, which stimulated the adenylate cyclase, in Bio14.6 ventricles were lower than the levels in ventricles of the F1B hamster strain, and decreased as the stage of cardiomyopathy progressed. Moreover, re-expression of fetal mRNA was observed in the ventricle of cardiomyopathic Syrian hamsters of the Bio14.6 strain. These results indicate that reprogramming of cardiac gene expression both of myofibrillar and nonmyofibrillar components might occur in the failing heart.
Katoh
Y
Y
Third Department of Internal Medicine, Faculty of Medicine, University of Tokyo, Japan.
Komuro
I
I
Yamaguchi
H
H
Yazaki
Y
Y
D000818:Animals; D000252:Calcium-Transporting ATPases / Q000235:genetics; D006332:Cardiomegaly / Q000503:physiopathology*; D006224:Cricetinae; D003971:Diastole; D004195:Disease Models, Animal; D005326:Fetal Proteins / Q000235:genetics; D019204:GTP-Binding Proteins / Q000235:genetics; D005786:Gene Expression Regulation; D006333:Heart Failure / Q000503:physiopathology*; D008297:Male; D008647:Mesocricetus; D009200:Myocardial Contraction; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D011919:Rats, Inbred Strains; D016212:Transforming Growth Factor beta / Q000235:genetics
D005326:Fetal Proteins; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D019204:GTP-Binding Proteins; D000252:Calcium-Transporting ATPases