Effects of age on c-fos and c-myc gene expression in response to hemodynamic stress in isolated perfused rat hearts.

年龄对离体灌注大鼠心脏血流动力学应激反应中 c-fos 和 c-myc 基因表达的影响。

基本信息

批准号：
03670433
负责人：
ISOYAMA Shogen
金额：
$ 1.15万
依托单位：
Tohoku University School of Medicine
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (C)
财政年份：
1991
资助国家：
日本
起止时间：
1991 至 1992
项目状态：
已结题

项目摘要

Using an ex vivo model we examined whether the age-associated modulation of proto-oncogene expression was due to the aging of the heart per se. In the two age groups of Wistar rats (2 and 18 months), expression of c-fos and c-myc genes was determined in isolated, isovolumically contracting hearts (balloon in the left ventricle) perfused with Tyrode's solution containing bovine serum and red blood cells. In both age groups, c-fos signal was detected at 30 min, increased further at 60 min, and declined at 120 min, while the c-myc signal was detected at 60 min and increased further 120 min after initiation of perfusion at 25 mm Hg of end-diastolic pressure (EDP). The expression of these genes by 60 min of relatively mild hemodynamic stress was depressed in old hearts compared to that in young hearts (c-fos at 0 (p<0.05), 5 (p<0.05) and 15 mm Hg of EDP (p<0.01); c-myc at 5 (p<0.05) and 15 mm Hg (p<0.05)). The age-associated differences in the expression of these genes were smaller under severe hemodynamic stress (25 mm Hg of EDP). Peak systolic and diastolic wall stress calculated from left ventricular pressure, cavity volume and muscle weight were similar in the two age groups. Thus, aging diminishes the expression of proto-oncogenes and seems to elevate the threshold at which hemodynamic stress to the heart results in a response at the gene level. The age-associated modulation is caused by aging of the heart per se.

使用离体模型，我们检查了与年龄相关的原癌基因表达调节是否是由于心脏本身的衰老所致。在 Wistar 大鼠的两个年龄组（2 个月和 18 个月）中，在用含有牛血清和红血的 Tyrode 溶液灌注的离体等容收缩心脏（左心室中的气球）中测定了 c-fos 和 c-myc 基因的表达细胞。在两个年龄组中，c-fos信号在30分钟时检测到，在60分钟时进一步增加，并在120分钟时下降，而c-myc信号在60分钟时检测到，并在25mm开始灌注后120分钟进一步增加舒张末压 (EDP) 汞柱。与年轻心脏相比，60 分钟相对温和的血流动力学应激后，这些基因的表达在老年心脏中降低（c-fos 为 0 (p<0.05)、5 (p<0.05) 和 15 mm Hg EDP (p <0.01)；c-myc 为 5 (p<0.05) 和 15 mm Hg (p<0.05))。在严重的血流动力学应激（EDP 25 mm Hg）下，这些基因的表达与年龄相关的差异较小。根据左心室压力、腔体积和肌肉重量计算得出的收缩期和舒张期壁应力峰值在两个年龄组中相似。因此，衰老会减少原癌基因的表达，并且似乎会提高心脏血流动力学应激导致基因水平反应的阈值。与年龄相关的调节是由心脏本身的老化引起的。