Hemodynamic regulation of tumor necrosis factor-alpha gene and protein expression in adult feline myocardium
Hemodynamic regulation of tumor necrosis factor-alpha gene and protein expression in adult feline myocardium
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DOI：
10.1161/01.res.81.2.187
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发表时间：
1997-08-01
影响因子：
20.1
通讯作者：
Mann, DL
中科院分区：
文献类型：
--
作者：
Kapadia, SR;Oral, H;Mann, DL
肿瘤坏死因子- α (tnf - α) mRNA和蛋白的生物合成在存在和不存在叠加血流动力学压力过载的成年猫心肌中进行了检测。短暂的体外血流动力学压力超载导致30分钟内新生tnf - α mRNA表达和60分钟内新生tnf - α蛋白产生；在正常灌注压力下灌注的心脏中均未检测到tnf - α mRNA和蛋白。此外，在压力过载心脏的肌细胞和非肌细胞类型中观察到tnf - α mRNA和蛋白质的生物合成。为了确定心肌的简单被动拉伸是否足以刺激tnf - α的生物合成，我们检测了拉伸和未拉伸乳头肌中tnf - α mRNA的表达。本研究表明，心肌拉伸是诱导tnf - α mRNA生物合成的充分刺激。心肌内产生tnf - α的功能意义是通过检测来自压力过载心脏和对照心脏的超液处理的离体收缩心肌细胞的细胞运动来确定的。这些研究表明，来自压力过载心脏的过充液处理的肌细胞运动受到抑制，而来自对照心脏的过充液处理的肌细胞运动正常。最后，生理条件下体内血流动力学压力超载也被证明会导致心肌内tnf - α mRNA的新生生物合成。总之，这项研究初步证明了成年哺乳动物心肌在体内和体外对血流动力学压力过载的反应中都表现出生物活性的tnf - α。
Tumor necrosis factor-alpha: (TNF-alpha) mRNA and protein biosynthesis were examined in adult feline myocardium in the presence and absence of superimposed hemodynamic pressure overloading. A brief period of hemodynamic pressure overloading ex vivo resulted in de novo TNF-alpha mRNA expression within 30 minutes and de novo TNF-alpha protein production within 60 minutes; neither TNF-alpha mRNA nor protein was detected in hearts perfused at normal perfusion pressures. Moreover, TNF-alpha mRNA and protein biosynthesis were observed in myocyte and nonmyocyte cell types in the pressure-overloaded hearts. To determine whether a simple passive stretch of the myocardium was a sufficient stimulus for TNF-alpha biosynthesis, we examined TNF-alpha mRNA expression in stretched and unstretched papillary muscles. This study showed that myocardial stretch was a sufficient stimulus for the induction of TNF-alpha mRNA biosynthesis. The functional significance of the intramyocardial production of TNF-alpha was determined by examining cell motion in isolated contracting cardiac myocytes treated with superfusates from pressure-overloaded and control hearts. These studies showed that cell motion was depressed in myocytes treated with superfusates from the pressure-overloaded hearts but was normal with the superfusates from the control hearts. Finally, hemodynamic pressure overloading in vivo under physiological conditions was also shown to result in de novo intramyocardial TNF-alpha mRNA biosynthesis. In conclusion, this study constitutes the initial demonstration that the adult mammalian myocardium elaborates biologically active TNF-alpha, both ex vivo and in vivo, in response to hemodynamic pressure overloading.