![]() Thus, the overall impact of the RAS is determined by the actual balance between the ACE–Ang II and ACE2–Ang (1–7) counterparts of the system ( Arendse et al., 2019). ACE2, a homolog of ACE, converts Ang II to Ang (1–7) which acts on the Mas receptor and has opposite effects to those of Ang II including vasodilator, antioxidant, and anti-inflammatory actions. The reason for the latter is that the angiotensin-converting enzyme 2 (ACE2), known to be the receptor of both SARS-CoV-1 and SARS-CoV-2 ( Li et al., 2003 Hoffmann et al., 2020 Zhou et al., 2020), might be overexpressed in patients taking ACEIs or ARBs potentially promoting the cellular uptake of the coronavirus in the airways.Īccording to the classical view, angiotensin II (Ang II or Ang (1–8)), produced by the angiotensin-converting enzyme (ACE), is the major element of the renin–angiotensin system (RAS) owing to its diverse effects predominantly mediated by the angiotensin type 1 (AT 1) receptor including vasoconstriction, a detrimental remodeling as well as oxidative stress in various tissues. Advanced age and cardiovascular comorbidities were confirmed to be associated with a severe form of the disease ( Zhang et al., 2020) and angiotensin-converting enzyme inhibitors (ACEIs), and angiotensin receptor blockers (ARBs) widely used in the treatment of cardiovascular diseases were implicated as well ( Diaz, 2020). Reports suggested that 1–3% of COVID-19 cases have a fatal outcome which prompted physicians and healthcare professionals to seek prognostic factors. At the time of writing this review, there are more than 40,000,000 confirmed cases and over 1,100,000 reported deaths ( WHO, 2020). ![]() Since then, the outbreak escalated to be a pandemic, causing devastation on all continents. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the pathogen of coronavirus disease 2019 (COVID-19), was first reported to cause human infection in Wuhan, China, in December 2019 ( Tan et al., 2020). This result should be interpreted in the light of the dual role of ACE2 being a promoter of viral entry to cells and a protective factor against oxidative damage in the lungs. The majority of these papers reported increased ACE2 levels in response to ACEI/ARB treatment. After a comprehensive search and selection, 27 animal studies investigating ACE2 expression in the context of ACEI and ARB were identified. The present study aimed to systematically review the relationship between ACEI/ARB administration and ACE2 expression in experimental models. This enzyme is also known as the receptor of SARS‐CoV‐2 promoting the cellular uptake of the virus in the airways, however, ACE2 itself proved to be protective in several experimental models of lung injury. These drugs have been reported to upregulate angiotensin converting enzyme 2 (ACE2) which produces Ang (1–7), the main counter-regulatory mediator of angiotensin II. Angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) are widely used in hypertension, heart failure and chronic kidney disease. Reports suggested that near 1–3% of COVID‐19 cases have a fatal outcome. Severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), the pathogen of coronavirus disease 2019 (COVID‐19), caused the outbreak escalated to pandemic. 6Department of Pharmacology, Faculty of Pharmacy, University of Pécs, Pécs, Hungary.5Szentágothai Research Centre, University of Pécs, Pécs, Hungary.4Institute for Translational Medicine, Medical School, University of Pécs, Pécs, Hungary.3Department of Anaesthesiology and Intensive Therapy, Medical School, University of Pécs, Pécs, Hungary.2Szentágothai Research Centre, Molecular Pharmacology Research Group, University of Pécs, Pécs, Hungary.1Department of Pharmacology and Pharmacotherapy, Medical School, University of Pécs, Pécs, Hungary.Gábor Kriszta 1,2, Zsófia Kriszta 1,3, Szilárd Váncsa 4,5, Péter Jenő Hegyi 4, Levente Frim 4, Bálint Erőss 4, Péter Hegyi 4,5, Gábor Pethő 1,6 † and Erika Pintér 1* †
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