Cellular interaction in pathogenesis of cardiac dysfuction

心力衰竭是一种进行性疾病，预后差，并伴有非自然心肌肥厚。肥大或衰竭心脏中基因表达的改变已被证实是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血清肿瘤坏死因子-α(TNF-α)浓度之间存在相关性，肿瘤坏死因子-α具有负性变力作用。然而，目前尚不清楚肿瘤坏死因子-α是否具有致病作用。在这项研究中，我们利用新生大鼠的心肌细胞，在体外研究了肿瘤坏死因子-α的作用。心肌细胞总蛋白浓度测定显示，FCS使单核细胞蛋白增加1.52倍，1和10 ng/ml的TNF-α使单核细胞蛋白分别增加1.24倍和1.18倍。与无血清对照组相比，加入1和10 ng/ml的肿瘤坏死因子-α使心肌细胞~(3 H)标记的苯丙氨酸掺入量分别增加1.92倍和2.07倍。1 ng/m l和10 ng/m l的肿瘤坏死因子-α对心钠素基因转录的促进作用分别是对照的1.21和1.72倍，β-肌球蛋白重链基因的转录促进作用分别是对照的1.17和1.37倍。结果表明，THF-α在转录水平促进心肌肥大，强烈表明肿瘤坏死因子-α加速了心力衰竭的疾病进程。

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.