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      Changes in myosin and creatine kinase mRNA levels with cardiac hypertrophy and hypothyroidism.

      Basic Research in Cardiology

      Animals, Rats, Inbred Strains, Rats, metabolism, RNA, Messenger, RNA, pharmacology, Propylthiouracil, Nucleic Acid Hybridization, genetics, Myosins, Myocardium, Male, Isoproterenol, Isoenzymes, chemically induced, Hypothyroidism, complications, Hypertension, Creatine Kinase, etiology, Cardiomegaly, Brain

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          Rats were treated with three methods which produce alterations in the expression of myosin isozymes: coarctation of the abdominal aorta, treatment with low doses of isoproterenol, and administration of propylthiouracil. The steady-state levels of the left ventricle mRNAs for alpha myosin heavy chain (alpha-MHC), beta myosin heavy chain (beta-MHC), M creatine kinase (MCK), and B creatine kinase (BCK) were then determined using Northern and slot blot hybridizations. Cardiac hypertrophy was induced by an acute systolic pressure overload, or beta adrenergic stimulation. At 7 days following systolic pressure overload, the induced cardiac hypertrophy was accompanied by alterations in the levels of MHC mRNAs, as has been previously reported. In RNA from left ventricles of treated animals alpha-MHC mRNA levels decreased by 15% by day 3 and 20% by day 7. In contrast, beta-MHC mRNA levels increased to 250% of control levels by day 3 and then declined to a value 150% of controls by day 7. Levels of MCK and BCK mRNAs showed little or no changes by day 3; at day 7 both MCK and BCK mRNAs showed decreases of 20% relative to controls. Cardiac hypertrophy induced by low doses of isoproterenol produced decreases of alpha-MHC mRNA levels to 70% of control values at day 3 and 50% at day 7. Over the same time periods there was an increase in the levels of the fetal mRNA isoform (beta-MHC) to 190%, then 130% of control values, respectively. At 3 days, both BCK and MCK mRNA levels had declined by approximately 20-25%. By 7 days, MCK mRNA levels had decreased by approximately 50% and BCK mRNA levels by 30%. Hypothyroidism induced by PTU treatment led to a 50% decrease in alpha-MHC mRNA levels by day 3, which then further decreased to 10% of control levels at day 7. beta-MHC mRNA levels increased to 350% of control levels at day 3 and then decreased to 275% of control levels at day 7. For creatine kinase mRNAs the level of the M isoform was increased by 30% at day 3, whereas there appeared to be no significant change in levels of B isoform mRNA at this time. At day 7 neither BCK nor MCK mRNA levels were significantly different from controls. These results show three treatments which produce an alteration in myosin mRNA isoforms produce little or no change in creatine kinase isoform mRNAs. Thus, the MHC and CK genes respond differently to either cardiac hypertrophy or a reduction in thyroid hormone levels.

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