Angiotensin-converting enzyme 2 (ACE2) is essential for SARS-CoV-2 cellular entry. Here we studied the effects of common comorbidities in severe COVID-19 on ACE2 expression. ACE2 levels (by enzyme activity and ELISA measurements) were determined in human serum, heart and lung samples from patients with hypertension (n = 540), heart transplantation (289) and thoracic surgery (n = 49). Healthy individuals (n = 46) represented the controls. Serum ACE2 activity was increased in hypertensive subjects (132%) and substantially elevated in end-stage heart failure patients (689%) and showed a strong negative correlation with the left ventricular ejection fraction. Serum ACE2 activity was higher in male (147%), overweight (122%), obese (126%) and elderly (115%) hypertensive patients. Primary lung cancer resulted in higher circulating ACE2 activity, without affecting ACE2 levels in the surrounding lung tissue. Male sex resulted in elevated serum ACE2 activities in patients with heart transplantation or thoracic surgery (146% and 150%, respectively). Left ventricular (tissular) ACE2 activity was unaffected by sex and was lower in overweight (67%), obese (62%) and older (73%) patients with end-stage heart failure. There was no correlation between serum and tissular (left ventricular or lung) ACE2 activities. Neither serum nor tissue (left ventricle or lung) ACE2 levels were affected by RAS inhibitory medications. Abandoning of ACEi treatment (non-compliance) resulted in elevated blood pressure without effects on circulating ACE2 activities. ACE2 levels associate with the severity of cardiovascular diseases, suggestive for a role of ACE2 in the pathomechanisms of cardiovascular diseases and providing a potential explanation for the higher mortality of COVID-19 among cardiovascular patients. Abandoning RAS inhibitory medication worsens the cardiovascular status without affecting circulating or tissue ACE2 levels.

血管紧张素转换酶 2 (ACE2) 对于 SARS-CoV-2 细胞进入至关重要。在这里，我们研究了重症 COVID-19 中常见合并症对 ACE2 表达的影响。在高血压 ( n  = 540)、心脏移植 (289) 和胸外科 ( n  = 49)患者的人血清、心脏和肺样本中测定 ACE2 水平（通过酶活性和 ELISA 测量）。健康个体（n = 46）代表控制。高血压受试者的血清 ACE2 活性增加（132%），而终末期心力衰竭患者的血清 ACE2 活性显着升高（689%），并且与左心室射血分数呈强负相关。男性 (147%)、超重 (122%)、肥胖 (126%) 和老年 (115%) 高血压患者的血清 ACE2 活性较高。原发性肺癌导致更高的循环 ACE2 活性，而不影响周围肺组织中的 ACE2 水平。男性导致心脏移植或胸外科手术患者血清 ACE2 活性升高（分别为 146% 和 150%）。左心室（组织）ACE2 活性不受性别影响，并且在患有终末期心力衰竭的超重（67%）、肥胖（62%）和老年（73%）患者中较低。血清和组织（左心室或肺）ACE2 活性之间没有相关性。血清和组织（左心室或肺）ACE2 水平均不受 RAS 抑制药物的影响。放弃 ACEi 治疗（不依从）导致血压升高，但对循环 ACE2 活性没有影响。ACE2 水平与心血管疾病的严重程度相关，提示 ACE2 在心血管疾病的病理机制中的作用，并为心血管患者中 COVID-19 的较高死亡率提供了潜在的解释。放弃 RAS 抑制药物会使心血管状况恶化，而不会影响循环或组织 ACE2 水平。血清和组织（左心室或肺）ACE2 水平均不受 RAS 抑制药物的影响。放弃 ACEi 治疗（不依从）导致血压升高，但对循环 ACE2 活性没有影响。ACE2 水平与心血管疾病的严重程度相关，提示 ACE2 在心血管疾病的病理机制中的作用，并为心血管患者中 COVID-19 的较高死亡率提供了潜在的解释。放弃 RAS 抑制药物会使心血管状况恶化，而不会影响循环或组织 ACE2 水平。血清和组织（左心室或肺）ACE2 水平均不受 RAS 抑制药物的影响。放弃 ACEi 治疗（不依从）导致血压升高，但对循环 ACE2 活性没有影响。ACE2 水平与心血管疾病的严重程度相关，提示 ACE2 在心血管疾病的病理机制中的作用，并为心血管患者中 COVID-19 的较高死亡率提供了潜在的解释。放弃 RAS 抑制药物会使心血管状况恶化，而不会影响循环或组织 ACE2 水平。提示ACE2在心血管疾病的病理机制中的作用，并为心血管患者中COVID-19的较高死亡率提供了潜在的解释。放弃 RAS 抑制药物会使心血管状况恶化，而不会影响循环或组织 ACE2 水平。提示ACE2在心血管疾病的病理机制中的作用，并为心血管患者中COVID-19的较高死亡率提供了潜在的解释。放弃 RAS 抑制药物会使心血管状况恶化，而不会影响循环或组织 ACE2 水平。