Saheb Sharif-Askari Narjes, Saheb Sharif-Askari Fatemeh, Al Heialy Saba, Hamoudi Rifat, Kashour Tarek, Hamid Qutayba, Halwani Rabih
Sharjah Institute of Medical Research, College of Medicine, University of Sharjah, Sharjah, United Arab Emirates.
College of Medicine, Mohammed Bin Rashid University, Dubai, United Arab Emirates.
Int J Cardiol Hypertens. 2020 Jun 6;6:100034. doi: 10.1016/j.ijchy.2020.100034. eCollection 2020 Sep.
Emerging epidemiological studies suggested that Renin-Angiotensin-Aldosterone system (RAAS) inhibitors may increase infectivity and severity of COVID-19 by modulating the expression of ACE2.
In silico analysis was conducted to compare the blood expression levels of SARS-CoV-2 entry genes between age and gender matched cohort of hypertensive patients versus control, and to determine the effect of common cardiovascular medications on the expression of COVID-19 receptors in vitro using primary human hepatocytes.
The transcriptomic analysis revealed a significant increase of ACE2 and TMPRSS2 in the blood of patients with hypertension. Treatment of primary human hepatocytes with captopril, but not enalapril, significantly increased ACE2 expression. A similar pattern of ACE2 expression was found following the in vitro treatments of rat primary cells with captopril and enalapril. Telmisartan, a second class RAAS inhibitors, did not affect ACE2 levels. We have also tested other cardiovascular medications that may be used alone, or in combination with RAAS inhibitors. Some of these medications increased TMPRSS2, while others, like furosemide, significantly reduced COVID-19 receptors.
The increase in ACE2 expression levels could be due to chronic use of RAAS inhibitors or alternatively caused by other hypertension-related factors or presence of other comorbidities. Treatment of common co-morbidities often require chronic use of multiple medications, which may result in an additive increase in the expression of ACE2 and TMPRSS2. Our data suggest that more research is needed to determine the effect of different medications, as well as medication combinations, on COVID-19 receptors.
新出现的流行病学研究表明，肾素-血管紧张素-醛固酮系统（RAAS）抑制剂可能通过调节血管紧张素转换酶2（ACE2）的表达来增加2019冠状病毒病（COVID-19）的感染性和严重程度。
进行了计算机分析，以比较年龄和性别匹配的高血压患者队列与对照组之间严重急性呼吸综合征冠状病毒2（SARS-CoV-2）进入基因的血液表达水平，并使用原代人肝细胞在体外确定常用心血管药物对COVID-19受体表达的影响。
转录组分析显示高血压患者血液中ACE2和跨膜丝氨酸蛋白酶2（TMPRSS2）显著增加。用卡托普利而非依那普利处理原代人肝细胞可显著增加ACE2表达。在用卡托普利和依那普利对大鼠原代细胞进行体外处理后，发现了类似的ACE2表达模式。第二类RAAS抑制剂替米沙坦不影响ACE2水平。我们还测试了其他可能单独使用或与RAAS抑制剂联合使用的心血管药物。其中一些药物增加了TMPRSS2，而其他药物，如呋塞米，则显著降低了COVID-19受体。
ACE2表达水平的增加可能是由于长期使用RAAS抑制剂，或者是由其他与高血压相关的因素或其他合并症的存在引起的。常见合并症的治疗通常需要长期使用多种药物，这可能导致ACE2和TMPRSS2表达的累加增加。我们的数据表明，需要更多的研究来确定不同药物以及药物组合对COVID-19受体的影响。
