scholarly journals Potential Roles of the Renin-Angiotensin System in the Pathogenesis and Treatment of COVID-19

2020 ◽  
Vol 2020 ◽  
pp. 1-7
Author(s):  
Ling Lu ◽  
Xiaomei Liu ◽  
Rong Jin ◽  
Renzheng Guan ◽  
Rongjun Lin ◽  
...  

The spread of pathogenic severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) poses a global health emergency. Based on the symptomatic treatment and supporting therapy, prevention of complications is the major treatment option. Therefore, it is necessary to illustrate the potential mechanisms for the pathogenesis of COVID-19. Angiotensin-converting enzyme 2 (ACE2), the major receptor of SARS-CoV-2, is one of the major members of the renin-angiotensin system (RAS). In this review, we aimed to summarize the crucial roles of ACE2 in the pathogenesis of COVID-19, followed by illustrating potential treatment options relating to ACE2 and the RAS.

TH Open ◽  
2020 ◽  
Vol 04 (02) ◽  
pp. e138-e144 ◽  
Author(s):  
Wolfgang Miesbach

AbstractThe activated renin–angiotensin system induces a prothrombotic state resulting from the imbalance between coagulation and fibrinolysis. Angiotensin II is the central effector molecule of the activated renin–angiotensin system and is degraded by the angiotensin-converting enzyme 2 to angiotensin (1–7). The novel coronavirus infection (classified as COVID-19) is caused by the new coronavirus SARS-CoV-2 and is characterized by an exaggerated inflammatory response that can lead to severe manifestations such as acute respiratory distress syndrome, sepsis, and death in a proportion of patients, mostly elderly patients with preexisting comorbidities. SARS-CoV-2 uses the angiotensin-converting enzyme 2 receptor to enter the target cells, resulting in activation of the renin–angiotensin system. After downregulating the angiotensin-converting enzyme 2, the vasoconstrictor angiotensin II is increasingly produced and its counterregulating molecules angiotensin (1–7) reduced. Angiotensin II increases thrombin formation and impairs fibrinolysis. Elevated levels were strongly associated with viral load and lung injury in patients with severe COVID-19. Therefore, the complex clinical picture of patients with severe complications of COVID-19 is triggered by the various effects of highly expressed angiotensin II on vasculopathy, coagulopathy, and inflammation. Future treatment options should focus on blocking the thrombogenic and inflammatory properties of angiotensin II in COVID-19 patients.


2021 ◽  
Vol 1 (1) ◽  
pp. 131-138
Author(s):  
Cosmin Andrei Cismaru ◽  
Gabriel Laurențiu Cismaru ◽  
Claudia Cristina Burz ◽  
Andreea Nutu ◽  
Ioana Berindan Neagoe

"Coronavirus disease 2019 (COVID-19) has become a serious healthcare problem, causing more than 2 million fatalities worldwide. Several treatments used for the management of chronic diseases such as hypertension, cardiovascular disease, diabetes and arthritis were shown to increase the expression of the receptor exploited by the virus, the angiotensin-converting enzyme 2 (ACE2), in vitro. This raises concerns on the safety of continuing such drugs or switching to other classes that don’t interfere with the receptor exploited by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Here we emphasize the mechanisms behind the regulation of ACE2 expression by several widely used drugs with possible interactions with COVID-19. Moreover, we discuss how the physiological mechanisms of attenuating inflammation and fibrosis can lead to increased expression of the receptor exploited by the virus and how this expression is further influenced be statins, propionate derivative nonsteroidal antiinflamatory drugs (NSAIDs) and renin-angiotensin system (RAS) blockers."


Hypertension ◽  
2020 ◽  
Vol 76 (3) ◽  
pp. 651-661 ◽  
Author(s):  
Ravindra K. Sharma ◽  
Bruce R. Stevens ◽  
Alexander G. Obukhov ◽  
Maria B. Grant ◽  
Gavin Y. Oudit ◽  
...  

Discovery of ACE2 (angiotensin-converting enzyme 2) revealed that the renin-angiotensin system has 2 counterbalancing arms. ACE2 is a major player in the protective arm, highly expressed in lungs and gut with the ability to mitigate cardiopulmonary diseases such as inflammatory lung disease. ACE2 also exhibits activities involving gut microbiome, nutrition, and as a chaperone stabilizing the neutral amino acid transporter, B 0 AT1, in gut. But the current interest in ACE2 arises because it is the cell surface receptor for the novel coronavirus, severe acute respiratory syndrome coronavirus-2, to infect host cells, similar to severe acute respiratory syndrome coronavirus-2. This suggests that ACE2 be considered harmful, however, because of its important other roles, it is paradoxically a potential therapeutic target for cardiopulmonary diseases, including coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus-2. This review describes the discovery of ACE2, its physiological functions, and its place in the renin-angiotensin system. It illustrates new analyses of the structure of ACE2 that provides better understanding of its actions particularly in lung and gut, shedding of ACE2 by ADAM17 (a disintegrin and metallopeptidase domain 17 protein), and role of TMPRSS2 (transmembrane serine proteases 2) in severe acute respiratory syndrome coronavirus-2 entry into host cells. Cardiopulmonary diseases are associated with decreased ACE2 activity and the mitigation by increasing ACE2 activity along with its therapeutic relevance are addressed. Finally, the potential use of ACE2 as a treatment target in COVID-19, despite its role to allow viral entry into host cells, is suggested.


2020 ◽  
Vol 126 (10) ◽  
pp. 1456-1474 ◽  
Author(s):  
Mahmoud Gheblawi ◽  
Kaiming Wang ◽  
Anissa Viveiros ◽  
Quynh Nguyen ◽  
Jiu-Chang Zhong ◽  
...  

Author(s):  
Annalise E Zemlin ◽  
Owen J Wiese

Since the first cases of atypical pneumonia linked to the Huanan Seafood Wholesale Market in Wuhan, China, were described in late December 2019, the global landscape has changed radically. In March 2020, the World Health Organization declared COVID-19 a global pandemic, and at the time of writing this review, just over three million individuals have been infected with more than 200,000 deaths globally. Numerous countries are in ‘lockdown’, social distancing is the new norm, even the most advanced healthcare systems are under pressure, and a global economic recession seems inevitable. A novel coronavirus (SARS-CoV-2) was identified as the aetiological agent. From experience with previous coronavirus epidemics, namely the severe acute respiratory syndrome (SARS) and Middle East Respiratory Syndrome (MERS) in 2004 and 2012 respectively, it was postulated that the angiotensin-converting enzyme-2 (ACE2) receptor is a possible port of cell entry. ACE2 is part of the renin-angiotensin system and is also associated with lung and cardiovascular disorders and inflammation. Recent studies have confirmed that ACE2 is the port of entry for SARS-CoV-2. Male sex, advanced age and a number of associated comorbidities have been identified as risk factors for infection with COVID-19. Many high-risk COVID-19 patients with comorbidities are on ACE inhibitors and angiotensin receptor blockers, and this has sparked debate about whether to continue these treatment regimes. Attention has also shifted to ACE2 being a target for future therapies or vaccines against COVID-19. In this review, we discuss COVID-19 and its complex relationship with ACE2.


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