Cellular interaction in pathogenesis of cardiac dysfuction

心力衰竭是一种预后不良的进展性疾病，并伴有非自然的心肌肥厚。在肥大或衰竭的心脏中改变的基因表达已被确定为是疾病进展的原因。另一方面，最近的证据表明心力衰竭的严重程度与具有负性肌力作用的肿瘤坏死因子α（TNF-α）的血清浓度之间存在相关性。然而，目前还不清楚TNF-α是否具有致病作用。在这项研究中，使用新生大鼠心肌细胞，我们研究了TNF-α在体外的影响。总心肌细胞蛋白质浓度的定量显示，与无血清对照相比，FCS使单核细胞蛋白质增加1.52倍，并且与对照值相比，浓度为1和10 ng/ml的TNF-α也分别使蛋白质增加1.24和1.18倍。与无血清对照组相比，加入1和10 ng/ml的TNF-α使心肌细胞培养液中^3H标记的苯丙氨酸掺入量分别增加了1.92和2.07倍。1 ng/ml和10 ng/ml TNF-α对心房钠尿肽基因转录的促进作用分别是对照组的1.21和1.72倍，对β-肌球蛋白重链基因转录的促进作用分别是对照组的1.17和1.37倍。结果，得出结论，TNF-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过程。

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.