ACE2 in the second act of COVID‐19 syndrome: Peptide dysregulation and possible correction with oestrogen

Abstract

The renin-angiotensin-aldosterone system (RAAS) comprises an endocrine cascade of vasoactive peptides to mineralocorticoids that orchestrate key processes in mammalian physiology. Notably, it preserves end-organ perfusion by regulating extracellular volume, sodium and water balance, and cardiovascular activity. The RAAS is also crucially involved in the inflammatory response, epithelial cell proliferation, angiogenesis and fibrosis. Two zinc metalloproteases are pivotal players in the RAAS, namely angiotensin-converting

Genetic and epigenetic control of ACE2 expression and its possible role in COVID‐19

“…Remarkably, apelin peptides specifically induce ACE2 expression through the action of APJR 25 . Given its actions, it has been hypothesized that apelin, and possibly its ACE2‐metabolized peptides, may be protective in COVID‐19 through their cardioprotective mechanisms 26,27 . ACE2 has been found associated with SLC6A19 in the brush border of epithelial intestinal cells and the proximal kidney tubules 28,29 .…”

The Role of Sex Hormones in the Disparity of COVID-19 Outcomes Based on Gender

“…However, in COVID-19, the clinical worsening and life-threatening phase rely right in an exaggerate inflammatory response with the so called "cytokine storm" for which a hyperactive immune system could be even detrimental. In addition, some [8], although not all [9], studies show that estrogens upregulate angiotensin-converting enzyme 2 (ACE2) that, on one hand, promotes the most favorable effects of renin-angiotensin system but, on the other hand, is the key enzyme that allow SARS-CoV-2 entering the pneumocytes and starting lung tissue damage and subsequent inflammatory events.…”

COVID-19 and hormonal contraception

“…The virus' spike protein binds to the ACE2 receptor to enter the cell and infect the body [ 3 ]. During this process, ACE2 is internalized and lost from the cell surface.…”

“…During this process, ACE2 is internalized and lost from the cell surface. ACE2 also plays an important role in reducing the progression of the disease, by intervening in the conversion of angiotensin II to angiotensin 1–7 and the degradation of other peptides important for vascular function and inflammatory modulation [ 3 ]. High concentrations of ACE2 counterbalance angiotensin II-induced inflammatory activation and reduce disease progression [ 3 ].…”

“…ACE2 also plays an important role in reducing the progression of the disease, by intervening in the conversion of angiotensin II to angiotensin 1–7 and the degradation of other peptides important for vascular function and inflammatory modulation [ 3 ]. High concentrations of ACE2 counterbalance angiotensin II-induced inflammatory activation and reduce disease progression [ 3 ]. Oestrogens and androgens modulate ACE2 activity differently; moreover, the response direction differs with the experimental conditions.…”