The pivotal link between ACE2 deficiency and SARS-CoV-2 infection.
Eur J Intern Med
; 76: 14-20, 2020 06.
Article
in English
| MEDLINE | ID: covidwho-88514
ABSTRACT
Angiotensin converting enzyme-2 (ACE2) receptors mediate the entry into the cell of three strains of coronavirus SARS-CoV, NL63 and SARS-CoV-2. ACE2 receptors are ubiquitous and widely expressed in the heart, vessels, gut, lung (particularly in type 2 pneumocytes and macrophages), kidney, testis and brain. ACE2 is mostly bound to cell membranes and only scarcely present in the circulation in a soluble form. An important salutary function of membrane-bound and soluble ACE2 is the degradation of angiotensin II to angiotensin1-7. Consequently, ACE2 receptors limit several detrimental effects resulting from binding of angiotensin II to AT1 receptors, which include vasoconstriction, enhanced inflammation and thrombosis. The increased generation of angiotensin1-7 also triggers counter-regulatory protective effects through binding to G-protein coupled Mas receptors. Unfortunately, the entry of SARS-CoV2 into the cells through membrane fusion markedly down-regulates ACE2 receptors, with loss of the catalytic effect of these receptors at the external site of the membrane. Increased pulmonary inflammation and coagulation have been reported as unwanted effects of enhanced and unopposed angiotensin II effects via the ACEâAngiotensin IIâAT1 receptor axis. Clinical reports of patients infected with SARS-CoV-2 show that several features associated with infection and severity of the disease (i.e., older age, hypertension, diabetes, cardiovascular disease) share a variable degree of ACE2 deficiency. We suggest that ACE2 down-regulation induced by viral invasion may be especially detrimental in people with baseline ACE2 deficiency associated with the above conditions. The additional ACE2 deficiency after viral invasion might amplify the dysregulation between the 'adverse' ACEâAngiotensin IIâAT1 receptor axis and the 'protective' ACE2âAngiotensin1-7âMas receptor axis. In the lungs, such dysregulation would favor the progression of inflammatory and thrombotic processes triggered by local angiotensin II hyperactivity unopposed by angiotensin1-7. In this setting, recombinant ACE2, angiotensin1-7 and angiotensin II type 1 receptor blockers could be promising therapeutic approaches in patients with SARS-CoV-2 infection.
Keywords
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Pneumonia, Viral
/
Receptors, Virus
/
Coronavirus Infections
/
Peptidyl-Dipeptidase A
/
Angiotensin II Type 1 Receptor Blockers
/
Pandemics
/
Betacoronavirus
Type of study:
Observational study
/
Prognostic study
Limits:
Humans
Language:
English
Journal:
Eur J Intern Med
Journal subject:
Internal Medicine
Year:
2020
Document Type:
Article
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