Expression of ACE2 receptor, soluble ACE2, Angiotensin I, Angiotensin II and Angiotensin (1-7), is modulated in COVID-19 patients

Abstract

Although SARS-CoV-2 is primarily a pulmonary-tropic virus, it is nonetheless responsible for multi-organ failure in patients with severe forms of COVID-19, particularly those with hypertension or cardiovascular disease. Infection requires virus binding to the angiotensin I converting enzyme 2 (ACE2) monocarboxypeptidase, a regulator of blood pressure homeostasis through its ability to catalyze the proteolysis of Angiotensin II (AngII) into Ang(1-7). Although assumed, it had not been proven so far whether the SARS-CoV-2 replication in COVID-19 patients could modulate the expression of the ACE2 receptor and/or the AngII plasma levels. We demonstrate here, that in COVID-19 patients the ACE2 mRNA expression is markedly reduced in circulating blood cells. This ACE2 gene dysregulation mainly affects the monocytes which also show a lower expression of membrane ACE2 protein. Moreover, a significant decrease in soluble ACE2 plasma levels is observed in COVID-19 patients, whereas the concentration of sACE2 returns to normal levels in patients recovered from COVID-19. In the plasma of COVID-19 patients, we also found an increase in AngI and AngII. On the other hand, the plasma levels of Ang(1-7) remains almost stable in COVID-19 patients. Despite the Ang(1-7) presence in the plasma of COVID-19 patients it seems insufficient to prevent the effects of massive AngII accumulation. These are the first direct evidence that the SARS-CoV-2 may affect the expression of blood pressure regulators with possible harmful consequences on COVID-19 outcome.

Perspectives and potential approaches for targeting neuropilin 1 in SARS-CoV-2 infection

“…One current study reported little to no expression of ACE2 on immune cells in human peripheral blood including B cells, NK cells, monocytes, dendritic cells, granulocytes, and all subtypes of T cells (Song et al 2020 ). However, ACE2 expression was induced or upregulated on CD3+ T cells obtained from infected patients while CD20+ B cells and the CD16+/HLA-DR+ monocytic/dendritic cells did not change a relatively low ACE2 level as compared to same cell populations obtained from healthy volunteers (Osman et al 2020 ).…”

ACE2: a key modulator of the renin-angiotensin system and pregnancy

“…Regardless, it is likely that SARS-CoV-2 infection in pregnant women has adverse effects on the balance between the ACE/Ang II/AT 1 R and ACE2/Ang-(1-7)/Mas axes in the placenta resulting in poor pregnancy outcomes for both the mother and fetus. Whether or not the virus alters the maternal systemic RAS pathways has not yet been investigated and in non-pregnant individuals reports on the effect of the virus on circulating ACE, ACE2 and Ang peptide levels are conflicting (96)(97)(98)(99)(100)(101)(102). Furthermore, since SARS-CoV-2 binding to ACE2 induces ADAM 17-dependent shedding of the ACE2 ectodomain (76) circulating levels are not likely to reflect local levels in tissues.…”