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Cellular interaction in pathogenesis of cardiac dysfuction

心功能不全发病机制中的细胞相互作用

基本信息

批准号：
07044253
负责人：
SASAYAMA Shigetake
金额：
$ 5.31万
依托单位：
KYOTO UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for international Scientific Research
财政年份：
1995
资助国家：
日本
起止时间：
1995 至无数据
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-07044253/
关键词：
cardiac hypertrophy heart failure cardiac function myocyte culture tumor necrosis factor cytokine

项目摘要

Heart failure is a progressive condition with poor prognosis, and it is accompanied by unnatural myocardial hypertrophy. Altered gene expression in the hypertrophied or failing heart has been identified as being responsible for the progression of the disease. On the other hand, recent evidence has indicated a correlation between the severity of heart failure and the serum concentration of tumor necrosis factor alpha (TNF-alpha), which has a negative inotropic effect. However, it is still unclear whether or not TNF-alpha has a pathogenic role. In this study, using cardiac myocytes from rat neonates, we studied the effects of TNF-alpha in vitro. Quanification of the total cardiac myocyte protein concentration revealed that FCS increased the monocyte protein by 1.52 times compared to that in the serum-free control, and TNF-alpha at the concentration of 1 and 10 ng/ml also increased the protein by 1.24 and 1.18 times, respectively, compared to the control value. The addition of TNF-alpha at 1 and 10 ng/ml increased the ^3H-labeled phenylalanine incorporation by 1.92 and 2.07 times in cardiac myocyte culture respectively, compared to that in the serum-free control. The enhancement of atrial natriuretic peptide gene transcription were 1.21 and 1.72 times control as 1 ng/ml and 10 ng/ml of TNF-alpha respectively, and those of beta-myosin heavy chain gene were 1.17 and 1.37 times control. As a result, it was concluded that THF-alpha promotes myocardial hypertrophy at the transcriptional level, strongly indicating that TNF-alpha accelerates the disease process of heart failure.

心力衰竭是一种预后不良的进行性疾病，并伴有非自然心肌肥厚。肥厚或衰竭心脏中基因表达的改变已被确定为导致疾病进展的原因。另一方面，最近的证据表明心力衰竭的严重程度与肿瘤坏死因子α（TNF-α）的血清浓度之间存在相关性，而肿瘤坏死因子α（TNF-α）具有负性肌力作用。然而，目前尚不清楚TNF-α是否具有致病作用。在这项研究中，我们使用新生大鼠的心肌细胞研究了 TNF-α 的体外作用。心肌细胞总蛋白浓度的定量显示，与无血清对照相比，FCS使单核细胞蛋白增加了1.52倍，与对照值相比，浓度为1和10ng/ml的TNF-α也分别使蛋白增加了1.24和1.18倍。与无血清对照相比，添加1和10ng/ml的TNF-α使心肌细胞培养物中^3H标记的苯丙氨酸掺入分别增加1.92和2.07倍。 TNF-α浓度为1 ng/ml和10 ng/ml时，心钠素基因转录增强作用分别是对照的1.21和1.72倍，β-肌球蛋白重链基因转录增强作用是对照的1.17和1.37倍。结果得出结论，THF-α在转录水平上促进心肌肥大，强烈表明TNF-α加速心力衰竭的疾病进程。