Spruth E, Zurbrügg H R, Warnecke C, Erdmann J, Pregla R, Pfautsch P, Hetzer R, Fleck E, Regitz-Zagrosek V
Internal Medicine/Cardiology, Humboldt Universität Berlin, Germany.
J Mol Med (Berl). 1999 Nov;77(11):804-10. doi: 10.1007/s001099900056.
The activity of the cardiac renin-angiotensin system is altered in human heart failure, but the regulatory mechanisms are unknown. We analyzed whether angiotensin-converting enzyme (ACE) mRNA expression in heart failure is altered in the atrial myocardium, and whether a correlation exists between atrial ACE mRNA expression and the parameters of left ventricular function. We also investigated whether the use of ACE inhibitors or the ACE I/D genotype modulates the atrial ACE mRNA content. For this purpose patients who were to undergo routine cardiac surgery were selected in a prospective manner according to left ventricular function and ACE inhibitor therapy. Samples of atrial myocardium were taken, and ACE mRNA expression was determined by internally standardized reverse transcription polymerase chain reaction. Atrial ACE mRNA expression did not differ in patients with left ventricular ejection fraction higher than 55% (2423+/-199 copies/ng RNA) and those with a value less than 45% (2661+/-143 copies/ng RNA, n.s.). ACE mRNA expression also did not differ in patients using ACE inhibitors (2585+/-175 copies/ng RNA) and those not using ACE inhibitors (2476+/-185 copies/ng RNA). Furthermore, atrial ACE mRNA expression was not affected by the ACE genotype (DD 2573+/-203, ID 2472+/-215, II 2563+/-249 copies/ng RNA). We conclude that the regulation of atrial ACE mRNA expression occurs predominantly by local mechanical or para- or autocrine factors.
人类心力衰竭时心脏肾素 - 血管紧张素系统的活性发生改变,但调节机制尚不清楚。我们分析了心力衰竭时心房肌中血管紧张素转换酶(ACE)mRNA表达是否改变,以及心房ACE mRNA表达与左心室功能参数之间是否存在相关性。我们还研究了使用ACE抑制剂或ACE I/D基因型是否会调节心房ACE mRNA含量。为此,根据左心室功能和ACE抑制剂治疗情况,前瞻性地选择了即将接受常规心脏手术的患者。采集心房肌样本,通过内部标准化逆转录聚合酶链反应测定ACE mRNA表达。左心室射血分数高于55%的患者(2423±199拷贝/ng RNA)与低于45%的患者(2661±143拷贝/ng RNA,无显著差异)的心房ACE mRNA表达无差异。使用ACE抑制剂的患者(2585±175拷贝/ng RNA)与未使用ACE抑制剂的患者(2476±185拷贝/ng RNA)的心房ACE mRNA表达也无差异。此外,心房ACE mRNA表达不受ACE基因型的影响(DD 2573±203,ID 2472±215,II 2563±249拷贝/ng RNA)。我们得出结论,心房ACE mRNA表达的调节主要由局部机械或旁分泌或自分泌因素介导。