Bauters C, Moalic J M, Bercovici J, Mouas C, Emanoil-Ravier R, Schiaffino S, Swynghedauw B
U 127 INSERM, Hopital Lariboisière, Paris, France.
J Mol Cell Cardiol. 1988 Feb;20(2):97-101. doi: 10.1016/s0022-2828(88)80023-3.
Chronic cardiac overload induces quantitative and qualitative changes of the phenotype which finally adapt the myocardium to its new functional requirements (Swynghedauw, 1986). It has been proposed that both stretch and enhanced isometric tension could trigger these modifications (Peterson and Lesch, 1972), but until now no real messenger has been found. In a search for signals which may account for these changes, we decided to investigate the expression of two proto-oncogenes, c-fos and c-myc, coding for nuclear proteins (review in Adamson, 1987) because several of their properties are consistent with their possessing a role in the transduction of extracellular growth signals to the cell interior. We report here that, in adult rat heart, expression of the c-fos and c-myc proto-oncogene was both sequentially and transitorily increased when, in a beating heart but not in an arrested heart, the coronary flow (and/or pressure) was augmented. This was studied in an isolated, coronary perfused heart preparation, a model in which the initial conditions of a cardiac overload may be mimicked in such a way that protein synthesis is stimulated by increasing the coronary perfusion pressure (Kira et al., 1984).
慢性心脏负荷过重会引起表型的数量和质量变化，最终使心肌适应其新的功能需求（斯温格道，1986年）。有人提出，牵张和增强的等长张力都可能引发这些改变（彼得森和莱施，1972年），但到目前为止尚未发现真正的信使分子。为了寻找可能解释这些变化的信号，我们决定研究两种原癌基因c-fos和c-myc的表达，它们编码核蛋白（亚当森，1987年综述），因为它们的一些特性与它们在将细胞外生长信号转导至细胞内部过程中发挥作用相一致。我们在此报告，在成年大鼠心脏中，当在跳动的心脏而非停搏的心脏中增加冠状动脉血流（和/或压力）时，c-fos和c-myc原癌基因的表达会依次且短暂地增加。这是在一个离体的、冠状动脉灌注的心脏标本中进行研究的，在这个模型中，可以模拟心脏负荷过重的初始条件，通过增加冠状动脉灌注压力来刺激蛋白质合成（基拉等人，1984年）。
