Cardiovascular medications and regulation of COVID-19 receptors expression

Narjes Saheb Sharif-Askari; Fatemeh Saheb Sharif-Askari; Saba Al Heialy; Rifat Hamoudi; Tarek Kashour; Qutayba Hamid; Rabih Halwani

doi:10.1016/j.ijchy.2020.100034

Cardiovascular medications and regulation of COVID-19 receptors expression

Int J Cardiol Hypertens. 2020 Jun 6:6:100034. doi: 10.1016/j.ijchy.2020.100034. eCollection 2020 Sep.

Authors

Narjes Saheb Sharif-Askari¹, Fatemeh Saheb Sharif-Askari¹, Saba Al Heialy^{2

3}, Rifat Hamoudi^{1

4}, Tarek Kashour⁵, Qutayba Hamid^{1

4

3}, Rabih Halwani^{1

4

6}

Affiliations

¹ Sharjah Institute of Medical Research, College of Medicine, University of Sharjah, Sharjah, United Arab Emirates.
² College of Medicine, Mohammed Bin Rashid University, Dubai, United Arab Emirates.
³ Meakins-Christie Laboratories, Research Institute of the McGill University Healthy Center, Montreal, Quebec, Canada.
⁴ Department of Clinical Sciences, College of Medicine, University of Sharjah, Sharjah, United Arab Emirates.
⁵ Department of Cardiology, King Fahad Cardiac Center, King Saud University Medical City, Riyadh, Saudi Arabia.
⁶ Prince Abdullah Ben Khaled Celiac Disease Research Chair, Department of Pediatrics, Faculty of Medicine, King Saud University, Saudi Arabia.

Abstract

Introduction: 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.

Methods: 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.

Results: 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.

Conclusions: 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.

Keywords: ACE2; Angiotensin converting enzyme inhibitors; COVID-19; Captopril; Cardiovascular medications; Enalapril; Hypertension; SARS-CoV-2; TMPRSS2.