Angiotensin-converting enzyme 2 and COVID-19 in cardiorenal diseases

Abstract

The rapid spread of the novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has brought into focus the key role of angiotensin-converting enzyme 2 (ACE2), which serves as a cell surface receptor required for the virus to enter cells. SARS-CoV-2 can decrease cell surface ACE2 directly by internalization of ACE2 bound to the virus and indirectly by increased ADAM17 (a disintegrin and metalloproteinase 17)-mediated shedding of ACE2. ACE2 is widely expressed in the heart, lungs, vasculature, kidney and the gastrointestinal (GI) tract, where it counteracts the deleterious effects of angiotensin II (AngII) by catalyzing the conversion of AngII into the vasodilator peptide angiotensin-(1-7) (Ang-(1-7)). The down-regulation of ACE2 by SARS-CoV-2 can be detrimental to the cardiovascular system and kidneys. Further, decreased ACE2 can cause gut dysbiosis, inflammation and potentially worsen the systemic inflammatory response and coagulopathy associated with SARS-CoV-2. This review aims to elucidate the crucial role of ACE2 both as a regulator of the renin–angiotensin system and a receptor for SARS-CoV-2 as well as the implications for Coronavirus disease 19 and its associated cardiovascular and renal complications.

Remdesivir, Renal Function and Short-Term Clinical Outcomes in Elderly COVID-19 Pneumonia Patients: A Single-Centre Study

“…Another possibility, that unfortunately we have been unable to test in patients participating in this survey, could be a decrease in ACE2 activity. 38 , 39 …”

“…Another possibility, that unfortunately we have been unable to test in patients participating in this survey, could be a decrease in ACE2 activity. 38,39 Matter of fact, in such cohort of patients with severe pneumonia and respiratory failure, no variable among those routinely checked was able to independently predict their short-term prognosis, and this was also true for the PaO 2 /FiO 2 ratio, an established indicator of respiratory failure severity in people carrying SARS CoV2, underlying the complexity of the disease, with systemic involvement of multiple tissues and organs.…”

Mild COVID-19 manifestation in multiple risk factor patient on methotrexate, who had been treated with UVB phototherapy and had sufficient plasma 25-OH-vitamin D3 level

“…Inappropriately excessive and uncontrolled inflammation more likely can result with the development of autodestrucitive cytokine storm, which is considered to be the final effector mechanism of tissue damage 4,6,10,11 . Obesity, insulin resistance and diabetes mellitus, as well as hypertension, are characterized by the presence of persistent low-intensity inflammation, which may be decisive underlying factor amplifying and perpetuating viral-induced inflammatory response [4][5][6][7][8][9][10][11] . Some authors also suggest pathogenetic involvement of immunogenic damage-associated molecular patterns (DAMPs), released as a consequence of preexisting disease 29 .…”

“…In most groups of risk patients, common mechanism favoring development of excessive inflammation and cytokine storm is persistently present proinflammatory milieu 7 . Such chronic proinflammatory state can arises either due to hypersecretion of proinflammatory adipokines in obese patients 7 , lack of anti-inflammatory signaling in diabetic and insulinresistant patients 7,8 or dysregulation of renin angiotensin system (RAS) with increased proinflammatory angiotensin II (Ang II) production in hypertensive patients 6,9,10 . Patients on immunosuppressive therapy are considered to be at risk due to the facilitated viral multiplication and dissemination during the initial phase, enabling in turn more vigorous ignition of hyperinflammatory phase 6,10,11 .…”

Ectodomain Shedding May Play a Pivotal Role in Disease Severity in COVID-19

“…Cell membrane-bound angiotensin-converting enzyme 2 (ACE2) has been identified as a binding site and entry receptor for the spike protein of SARS-CoV-2. After the (1)(2)(3)(4)(5)(6)(7). Angiotensin II binds to angiotensin II type 1 and 2 receptors (AT1 and AT2), leading to vasoconstriction, but angiotensin (1-7) binds to the MAS receptor, leading to vasodilation.…”