COVID-19: Critical Role of Angiotensin 1-7 in ACE2 Modulation

Abstract

With the declaration of Novel Coronavirus Disease 2019 (COVID-19) as pandemic by World Health Organization (WHO), many countries have taken drastic measure to enforce movement control to curb COVID-19 outbreak. On 23 January 2020, it was reported that Malaysia had 4 patients suspected to have contracted the COVID-19. On the same day, Singapore confirmed its first case of COVID-19. 1 The first confirmed COVID-19 case reported in Malaysia was on 24 January 2020. To date, WHO has reported a total of 5.6 million confirmed cases, with 353,373 confirmed deaths among 216 countries around the world. 2 Current evidence suggests that COVID-19 patients could develop rapidly worsening respiratory failure and acute respiratory distress syndrome (ARDS). 3 Similar to SAR-Cov (Severe Acute Respiratory Syndrome Coronavirus), COVID-19 is believed to be using the same entry point of Angiotensin Converting Enzyme 2 (ACE2) into the human host cells. 4,5 ACE2 is a carboxymonopeptidase that cleaves at the carboxy-terminal (C-terminal) end of a protein or peptide [6], and is expressed on respiratory and intestinal epithelial cells, endothelial cells, renal tubule cells and immune cells. 6-10 Tipnis et al (2000) also reported that the mammalian homologue of ACE has implications on cardiovascular and renal function. 11 Up to 96% of ACE2 is available as membrane-bound enzyme, and the minority of ACE2 (1-4%) presents as a soluble form in blood, urine, and other body fluids. 12,13 Additionally, the latest study by Wan et al (2020) reported that COVID-19 uses the same receptor-binding motif, as SAR-Cov that directly contacts with ACE2. 14 There is an intrinsically high renin angiotensin system (RAS) activity in the lungs, creating a relatively higher concentration of ACE2 in the organ. Interestingly, Angiotensin Converting Enzyme (ACE) inhibitors, which are commonly prescribed for hypertension treatment, antagonise specifically the effect of ACE, but not ACE2. [15] ACE2 plays an important role in RAS, by converting Angiotensin II to Angiotensin

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“…As this pandemic continues to evolve, researchers are learning more about SARS-CoV-2 every day, including the fact that it can be transmitted from symptomatic, presymptomatic and asymptomatic people infected with COVID-19 [4] . Studies have shown that COVID-19 is primarily transmitted from symptomatic people to people who are in close contact through respiratory droplets, by direct contact with infected persons or by contact with contaminated objects and surfaces [5] .…”

Role of the Renin–Angiotensin–Aldosterone and Kinin–Kallikrein Systems in the Cardiovascular Complications of COVID-19 and Long COVID

“…Ang(1-9) mediates its actions via the AT 2 R and produces the protective responses such as anti-fibrotic and anti-inflammatory effects [ 70 ]. Moreover, Ang(1-7) has been reported to bind to another GPCR, the Mas receptor (MasR), which can exert NO-dependent vasorelaxation and protect against cardiac remodelling; Ang(1-7) also acts as a β-arrestin biased agonist at AT 1 Rs [ 71 , 72 , 73 ]. This induces AT 1 R desensitisation and internalisation, which attenuates the Ang II mediated cardiovascular dysfunction [ 57 ].…”

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“…The spike glycoprotein at the N-terminal region of SARS-CoV-2 acts as a receptor binding domain which binds to the human angiotensin converting enzyme 2 (ACE2) of the host cell. This leads to fusion between viral and host cell membranes to allow entry of coronavirus into target host cells [ 4 ]. Upon being infected with SARS-CoV-2, patients may present without symptoms or with symptoms, ranging from mild, moderate, severe to critical, with clinical classifications outlined by the Chinese National Health Committee [ 5 ].…”