Effects of triiodo-thyronine on angiotensin-induced cardiomyocyte hypertrophy: reversal of increased beta-myosin heavy chain gene expression.
Thyroid hormone-induced cardiac hypertrophy is similar to that observed in physiological hypertrophy, which is associated with high cardiac contractility and increased alpha-myosin heavy chain (alpha-MHC, the high ATPase activity isoform) expression. In contrast, angiotensin II (Ang II) induces an increase in myocardial mass with a compromised contractility accompanied by a shift from alpha-MHC to the fetal isoform beta-MHC (the low ATPase activity isoform), which is considered as a pathological hypertrophy and inevitably leads to the development of heart failure. The present study is designed to assess the effect of thyroid hormone on angiotensin II-induced hypertrophic growth of cardiomyocytes in vitro. Cardiomyocytes were prepared from hearts of neonatal Wistar rats. The effects of Ang II and 3,3',5-triiodo-thyronine (T3) on incorporations of [3H]-thymine and [3H]-leucine, MHC isoform mRNA expression, PKC activity, and PKC isoform protein expression were studied. Ang II enhanced [3H]-leucine incorporation, beta-MHC mRNA expression, PKC activity, and PKCepsilon expression and inhibited alpha-MHC mRNA expression in cardiomyocytes. T3 treatment prevented Ang II-induced increases in PKC activity, PKCepsilon, and beta-MHC mRNA overexpression and favored alpha-MHC mRNA expression. Thyroid hormone appears to be able to reprogram gene expression in Ang II-induced cardiac hypertrophy, and a PKC signal pathway may be involved in such remodeling process.
Wang
Baohua
B
Department of Pathophysiology, School of Medicine, Wuhan University, Wuhan 430071, P.R. China.
Ouyang
Jingping
J
Xia
Zhengyuan
Z
D000809:Angiotensins; D000818:Animals; D000831:Animals, Newborn; D002478:Cells, Cultured; D005786:Gene Expression Regulation / Q000187:drug effects; D006984:Hypertrophy / Q000139:chemically induced / Q000517:prevention & control*; D007930:Leucine / Q000378:metabolism; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D018995:Myosin Heavy Chains / Q000235:genetics / Q000378:metabolism*; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D011493:Protein Kinase C / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013941:Thymine / Q000378:metabolism; D014284:Triiodothyronine / Q000494:pharmacology*
D000809:Angiotensins; C000594638:MYH7 protein, rat; D020033:Protein Isoforms; D012333:RNA, Messenger; D014284:Triiodothyronine; D011493:Protein Kinase C; D018995:Myosin Heavy Chains; D007930:Leucine; D013941:Thymine