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RAAS,ACE2 and COVID-19; a mechanistic review

Authors:	Ahmed Elshafei Emad Gamil Khidr Ahmed A El-Husseiny Maher H Gomaa

Institution:	Biochemistry and Molecular Biology Department, Faculty of Pharmacy, Al-Azhar University, Nasr City 11231, Cairo, Egypt

Abstract:	The use of angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) in coronavirus disease 2019 (COVID-19) patients has been claimed as associated with the risk of COVID-19 infection and its subsequent morbidities and mortalities. These claims were resulting from the possibility of upregulating the expression of angiotensin-converting enzyme 2 (ACE2), facilitation of SARS-CoV-2 entry, and increasing the susceptibility of infection in such treated cardiovascular patients. ACE2 and renin-angiotensin-aldosterone system (RAAS) products have a critical function in controlling the severity of lung injury, fibrosis, and failure following the initiation of the disease. This review is to clarify the mechanisms beyond the possible deleterious effects of angiotensin II (Ang II), and the potential protective role of angiotensin 1–7 (Ang 1–7) against pulmonary fibrosis, with a subsequent discussion of the latest updates on ACEIs/ARBs use and COVID-19 susceptibility in the light of these mechanisms and biochemical explanation.

Keywords:	COVID-19 ACE2 Angiotensin II Angiotensin 1–7 ACEIs ARBs ACE1"} {"#name":"keyword" "$":{"id":"k0040"} "$$":[{"#name":"text" "_":"angiotensin-converting enzyme 1 ACE2"} {"#name":"keyword" "$":{"id":"k0050"} "$$":[{"#name":"text" "_":"angiotensin-converting enzyme 2 ACEIs"} {"#name":"keyword" "$":{"id":"k0060"} "$$":[{"#name":"text" "_":"angiotensin-converting enzyme inhibitors AEC-II"} {"#name":"keyword" "$":{"id":"k0070"} "$$":[{"#name":"text" "_":"alveolar epithelial type II cells Ang 1-7"} {"#name":"keyword" "$":{"id":"k0080"} "$$":[{"#name":"text" "_":"angiotensin 1-7 Ang 1-9"} {"#name":"keyword" "$":{"id":"k0090"} "$$":[{"#name":"text" "_":"angiotensin 1-9 AngI"} {"#name":"keyword" "$":{"id":"k0100"} "$$":[{"#name":"text" "_":"angiotensin I AngII"} {"#name":"keyword" "$":{"id":"k0110"} "$$":[{"#name":"text" "_":"angiotensin II ARBs"} {"#name":"keyword" "$":{"id":"k0120"} "$$":[{"#name":"text" "_":"angiotensin receptor blockers AT1R"} {"#name":"keyword" "$":{"id":"k0130"} "$$":[{"#name":"text" "_":"angiotensin type 1 receptor AT2R"} {"#name":"keyword" "$":{"id":"k0140"} "$$":[{"#name":"text" "_":"angiotensin type 2 receptor COVID-19"} {"#name":"keyword" "$":{"id":"k0150"} "$$":[{"#name":"text" "_":"coronavirus disease 2019 CVD"} {"#name":"keyword" "$":{"id":"k0160"} "$$":[{"#name":"text" "_":"cardiovascular disease ERK"} {"#name":"keyword" "$":{"id":"k0170"} "$$":[{"#name":"text" "_":"extracellular signal-regulated kinase ICU"} {"#name":"keyword" "$":{"id":"k0180"} "$$":[{"#name":"text" "_":"intensive care unit MAPK"} {"#name":"keyword" "$":{"id":"k0190"} "$$":[{"#name":"text" "_":"mitogen-activated protein kinase miR-21"} {"#name":"keyword" "$":{"id":"k0200"} "$$":[{"#name":"text" "_":"microRNA-21 NLRP3"} {"#name":"keyword" "$":{"id":"k0210"} "$$":[{"#name":"text" "_":"(NOD LRR and pyrin domain-containing protein 3) RAAS"} {"#name":"keyword" "$":{"id":"k0220"} "$$":[{"#name":"text" "_":"renin-angiotensin-aldosterone system TGF-β"} {"#name":"keyword" "$":{"id":"k0230"} "$$":[{"#name":"text" "_":"transforming growth factor-beta
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