Imamura S, Matsuoka R, Hiratsuka E, Kimura M, Nakanishi T, Nishikawa T, Furutani Y, Takao A
Research Division Heart Institute of Japan, Tokyo.
Am J Physiol. 1991 Jan;260(1 Pt 2):H73-9. doi: 10.1152/ajpheart.1991.260.1.H73.
Distribution of cardiac myosin heavy-chain (MHC) isozymes is regulated during development by hemodynamic change and hormonal stimuli. To understand the evolution of cardiac hypertrophy and the underlying processes, the interaction between acute or chronic cardiac over-loading and serum thyroid hormone levels was studied. Biochemical, physiological, and pathological studies were performed using coarctated (Coa) rats with or without administration of thyroid hormone (Thy) and on sham-operated (Sham) rats and normal rats with or without administration of Thy. The results showed that 1) although serum Thy levels in Coa and Sham rats were nearly the same at all timing points, a significant induction of beta-MHC mRNA and isozyme occurred in Coa rats; 2) in Coa rats where Thy was administered, there was no increase in beta-MHC mRNA and isozyme as seen in Coa rats, and this level was nearly the same as in Sham rats, whereas serum Thy levels were significantly high, as in the normals with administration of Thy; and 3) 77 days after surgery, the hypertrophy was completed, judging from pathological findings at this time, and beta-MHC mRNA and isozyme reached similar levels in all groups, except for the normals with administration of Thy. These results demonstrate the following: 1) the MHC isoform transitions induced by pressure overload are not induced by decreases in serum Thy levels, and the regulation of MHC gene expression is responsive to other triggers in addition to Thy; and 2) the first adaptational process of the heart to hemodynamic overload is the MHC isoform transition, and the second adaptational process of that is the hypertrophy itself.
心肌肌球蛋白重链（MHC）同工酶的分布在发育过程中受血流动力学变化和激素刺激的调节。为了解心肌肥大的演变及其潜在机制，研究了急性或慢性心脏负荷过重与血清甲状腺激素水平之间的相互作用。使用接受或未接受甲状腺激素（Thy）的缩窄（Coa）大鼠以及假手术（Sham）大鼠和接受或未接受Thy的正常大鼠进行了生化、生理和病理学研究。结果表明：1）尽管Coa大鼠和Sham大鼠在所有时间点的血清Thy水平几乎相同，但Coa大鼠中β-MHC mRNA和同工酶有显著诱导；2）在给予Thy的Coa大鼠中，β-MHC mRNA和同工酶没有像Coa大鼠那样增加，且该水平与Sham大鼠几乎相同，而血清Thy水平显著升高，与给予Thy的正常大鼠一样；3）手术后77天，从此时的病理结果判断肥大已完成，除给予Thy的正常大鼠外，所有组的β-MHC mRNA和同工酶达到相似水平。这些结果表明：1）压力过载诱导的MHC亚型转变不是由血清Thy水平降低引起的，MHC基因表达的调节除Thy外还对其他触发因素有反应；2）心脏对血流动力学过载的第一个适应性过程是MHC亚型转变，第二个适应性过程是肥大本身。
