Lebek Simon, Tafelmeier Maria, Messmann Rebecca, Provaznik Zdenek, Schmid Christof, Maier Lars S, Birner Christoph, Arzt Michael, Wagner Stefan
Department of Internal Medicine II, University Hospital Regensburg, Regensburg, Germany.
Department of Cardiothoracic Surgery, University Hospital Regensburg, Regensburg, Germany.
Eur J Heart Fail. 2020 Dec;22(12):2248-2257. doi: 10.1002/ejhf.2020. Epub 2020 Oct 20.
Coronavirus disease 2019 (COVID-19) is a widespread pandemic with an increased morbidity and mortality, especially for patients with cardiovascular diseases. Angiotensin-converting enzyme 2 (ACE2) has been identified as necessary cell entry point for SARS-CoV-2. Previous animal studies have demonstrated an increased ACE2 expression following treatment with either angiotensin-converting enzyme inhibitors (ACEi) or angiotensin II receptor blockers (ARB) that have led to a massive precariousness regarding the optimal cardiovascular therapy during this pandemic.
We have measured ACE2 mRNA expression using real-time quantitative polymerase chain reaction in atrial biopsies of 81 patients undergoing coronary artery bypass grafting and we compared 62 patients that received ACEi/ARB vs. 19 patients that were not ACEi/ARB-treated. We found atrial ACE2 mRNA expression to be significantly increased in patients treated with an ACEi or an ARB, independent of potential confounding comorbidities. Interestingly, the cardiac ACE2 mRNA expression correlated significantly with the expression in white blood cells of 22 patients encouraging further evaluation if the latter may be used as a surrogate for the former. Similarly, analysis of 18 ventricular biopsies revealed a significant and independent increase in ACE2 mRNA expression in patients with end-stage heart failure that were treated with ACEi/ARB. On the other hand, cardiac unloading with a left ventricular assist device significantly reduced ventricular ACE2 mRNA expression.
Treatment with ACEi/ARB is independently associated with an increased myocardial ACE2 mRNA expression in patients with coronary artery disease and in patients with end-stage heart failure. Further trials are needed to test whether this association is deleterious for patients with COVID-19, or possibly protective. Nevertheless, haemodynamic factors seem to be equally important for regulation of cardiac ACE2 mRNA expression.
2019冠状病毒病（COVID-19）是一种广泛流行的大流行病，发病率和死亡率都有所增加，尤其是对于心血管疾病患者。血管紧张素转换酶2（ACE2）已被确定为严重急性呼吸综合征冠状病毒2（SARS-CoV-2）进入细胞的必要位点。先前的动物研究表明，使用血管紧张素转换酶抑制剂（ACEi）或血管紧张素II受体阻滞剂（ARB）治疗后，ACE2表达会增加，这在此次大流行期间引发了关于最佳心血管治疗的大量不稳定因素。
我们使用实时定量聚合酶链反应测量了81例接受冠状动脉搭桥术患者心房活检组织中ACE2 mRNA的表达，并比较了62例接受ACEi/ARB治疗的患者与19例未接受ACEi/ARB治疗的患者。我们发现，接受ACEi或ARB治疗的患者心房ACE2 mRNA表达显著增加，且不受潜在混杂合并症的影响。有趣的是，心脏ACE2 mRNA表达与22例患者白细胞中的表达显著相关，这促使进一步评估后者是否可作为前者的替代指标。同样，对18例心室活检组织的分析显示，接受ACEi/ARB治疗的终末期心力衰竭患者的ACE2 mRNA表达显著且独立增加。另一方面，使用左心室辅助装置进行心脏卸载可显著降低心室ACE2 mRNA表达。
在冠状动脉疾病患者和终末期心力衰竭患者中，使用ACEi/ARB治疗与心肌ACE2 mRNA表达增加独立相关。需要进一步试验来检验这种关联对COVID-19患者是有害还是可能具有保护作用。然而，血流动力学因素似乎对心脏ACE2 mRNA表达的调节同样重要。
