Gullestad L, Haywood G, Aass H, Ross H, Yee G, Ueland T, Geiran O, Kjekshus J, Simonsen S, Bishopric N, Fowler M
Falk Cardiovascular Research Center, Stanford University School of Medicine, CA 94305-5246, USA.
Cardiovasc Res. 1998 May;38(2):340-7. doi: 10.1016/s0008-6363(98)00015-7.
Cardiac hypertrophy appears early after heart transplantation, and may represent a myocardial response to injury. Recent evidence suggests that angiotensin II (Ang II) may promote growth through the AT1 and inhibit growth through the AT2 receptor subtypes. We therefore asked whether hypertrophy after heart transplantation is characterized by alterations in Ang II receptor gene expression.
The expression of Ang II receptor subtypes. AT1 and AT2, was analyzed in right ventricular endomyocardial biopsies taken from 10 human donor hearts prior to implantation (controls) and from 17 heart transplant recipients, 11 studied during annual evaluation (> 1 year after transplantation) and 6 one week after transplantation. Competitive reverse transcription polymerase chain reaction (RT-PCR) was performed using synthetic RNA internal standards for both receptor subtypes.
AT1 and AT2 receptor mRNAs were detected in all samples. AT1 receptor mRNA decreased 4.5 fold (p < 0.01) and AT2 receptor mRNA 4.2 fold (p < 0.001) in transplant patients compared with controls. In the subgroup of patients examined one week after surgery AT1 was reduced relative to AT2 receptor mRNA, resulting in an altered ratio of AT1 to AT2 early after transplantation. There was no correlation between Ang II receptor levels and left ventricular wall thickness, and the decrease in receptor level did not correlate with any hemodynamic parameters, cyclosporine blood levels, or plasma renin, Ang II or pANP, except for a negative correlation between AT2 mRNA and plasma renin (r = -0.49, p = 0.05).
Contrary to our expectations, mRNA for both Ang II receptors was downregulated after heart transplantation. The cause of myocardial hypertrophy after heart transplantation is still unclear, but the hypertrophy does not appear to be driven by increased transcription of the AT1 receptor.
心脏移植后早期即出现心脏肥大，这可能是心肌对损伤的一种反应。最近的证据表明，血管紧张素II（Ang II）可通过AT1受体促进生长，并通过AT2受体亚型抑制生长。因此，我们探讨心脏移植后的肥大是否以Ang II受体基因表达改变为特征。
分析了10例人类供体心脏植入前（对照组）及17例心脏移植受者右心室心内膜活检组织中Ang II受体亚型AT1和AT2的表达。11例在年度评估时（移植后>1年）进行研究，6例在移植后1周进行研究。使用两种受体亚型的合成RNA内标进行竞争性逆转录聚合酶链反应（RT-PCR）。
所有样本均检测到AT1和AT2受体mRNA。与对照组相比，移植患者的AT1受体mRNA下降4.5倍（p<0.01），AT2受体mRNA下降4.2倍（p<0.001）。在术后1周检查的患者亚组中，AT1相对于AT2受体mRNA减少，导致移植后早期AT1与AT2的比例改变。Ang II受体水平与左心室壁厚度之间无相关性，受体水平的降低与任何血流动力学参数、环孢素血药浓度或血浆肾素、Ang II或pANP均无相关性，但AT2 mRNA与血浆肾素呈负相关（r=-0.49，p=0.05）。
与我们的预期相反，心脏移植后两种Ang II受体的mRNA均下调。心脏移植后心肌肥大的原因仍不清楚，但肥大似乎不是由AT1受体转录增加驱动的。
