Effects of SARS-CoV-2 on Cardiovascular System: The Dual Role of Angiotensin-Converting Enzyme 2 (ACE2) as the Virus Receptor and Homeostasis Regulator-Review

Abstract

Angiotensin-converting enzyme 2 (ACE2) is the entry receptor for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), the cause of Coronavirus Disease-2019 (COVID-19) in humans. ACE-2 is a type I transmembrane metallocarboxypeptidase expressed in vascular endothelial cells, alveolar type 2 lung epithelial cells, renal tubular epithelium, Leydig cells in testes and gastrointestinal tract. ACE2 mediates the interaction between host cells and SARS-CoV-2 spike (S) protein. However, ACE2 is not only a SARS-CoV-2 receptor, but it has also an important homeostatic function regulating renin-angiotensin system (RAS), which is pivotal for both the cardiovascular and immune systems. Therefore, ACE2 is the key link between SARS-CoV-2 infection, cardiovascular diseases (CVDs) and immune response. Susceptibility to SARS-CoV-2 seems to be tightly associated with ACE2 availability, which in turn is determined by genetics, age, gender and comorbidities. Severe COVID-19 is due to an uncontrolled and excessive immune response, which leads to acute respiratory distress syndrome (ARDS) and multi-organ failure. In spite of a lower ACE2 expression on cells surface, patients with CVDs have a higher COVID-19 mortality rate, which is likely driven by the imbalance between ADAM metallopeptidase domain 17 (ADAM17) protein (which is required for cleavage of ACE-2 ectodomain resulting in increased ACE2 shedding), and TMPRSS2 (which is required for spike glycoprotein priming). To date, ACE inhibitors and Angiotensin II Receptor Blockers (ARBs) treatment interruption in patients with chronic comorbidities appears unjustified. The rollout of COVID-19 vaccines provides opportunities to study the effects of different COVID-19 vaccines on ACE2 in patients on treatment with ACEi/ARB.

CD147 antibody specifically and effectively inhibits infection and cytokine storm of SARS-CoV-2 and its variants delta, alpha, beta, and gamma

“…CD147 is expressed on various types of proinflammatory cells including Th17 cells, neutrophils, NK cells, 48 , 49 where ACE2 is rarely expressed. 50 Thus, SARS-CoV-2-infected hCD147 transgenic mice well recapitulate the symptoms of COVID-19 pneumonia, providing a good model for studying the pathogenic mechanism and pharmacodynamics of agents against COVID-19.…”

Susceptibility of β-Thalassemia Heterozygotes to COVID-19

“…CVS control is exerted through classical RAS inducing vasoconstriction via renin processed ANGII vasoconstrictors and counterbalancing non-classical RAS inducing vasodilation via ACE2 converted ANG1-7 vasodilators [23]. SARS-CoV-2 inhibits ACE2 expression and deranges CVS homeostasis [24]. Current strategies for COVID-19 treatment aim to suppress SARS-CoV-2 main protease activity, required to release active viral protein products and induce ACE2 expression [25].…”

Letter to the Editor concerning: pulmonary artery trunk enlargement on admission as a predictor of mortality in in-hospital patients with COVID-19

“…It would be helpful to know if the study being purely anatomical was a limitation and reduced the applications. Including symptoms and laboratory values related to inflammation, could provide valuable data in a similar study, such as this one reported by Aleksova et al [ 4 ].…”