tetano
Editor, Senior Moderator
Heart Lung Circ
. 2020 Dec 9;S1443-9506(20)31538-9.
doi: 10.1016/j.hlc.2020.11.008. Online ahead of print.
The Counter Regulatory Axis of the Lung Renin-Angiotensin System in Severe COVID-19: Physiopathology and Clinical Implications
Filippos Triposkiadis[SUP] 1 [/SUP], Randall C Starling[SUP] 2 [/SUP], Andrew Xanthopoulos[SUP] 3 [/SUP], Javed Butler[SUP] 4 [/SUP], Harisios Boudoulas[SUP] 5 [/SUP]
Affiliations
Abstract
The severe acute respiratory syndrome coronavirus (SARS-CoV)-2, which is responsible for coronavirus disease 2019 (COVID-19), uses angiotensin (ANG)-converting enzyme 2 (ACE2) as the entrance receptor. Although most COVID-19 cases are mild, some are severe or critical, predominantly due to acute lung injury. It has been widely accepted that a counter regulatory renin-angiotensin system (RAS) axis including the ACE2/ANG [1-7]/Mas protects the lungs from acute lung injury. However, recent evidence suggests that the generation of protective ANG [1-7] in the lungs is predominantly mediated by proinflammatory prolyloligopeptidase (POP), which has been repeatedly demonstrated to be involved in lung pathology. This review contends that acute lung injury in severe COVID-19 is characterised by a) ACE2 downregulation and malfunction (inflammatory signalling) due to viral occupation, and b) dysregulation of the protective RAS axis, predominantly due to increased activity of proinflammatory POP. It follows that a reasonable treatment strategy in COVID-19-related acute lung injury would be delivering functional recombinant (r) ACE2 forms to trap the virus. Additionally, or alternatively to rACE2 delivery, the potential benefits resulting from lowering POP activity should also be explored. These treatment strategies deserve further investigation.
Keywords: Acute lung injury; Coronavirus disease 2019; Renin-angiotensin system.
. 2020 Dec 9;S1443-9506(20)31538-9.
doi: 10.1016/j.hlc.2020.11.008. Online ahead of print.
The Counter Regulatory Axis of the Lung Renin-Angiotensin System in Severe COVID-19: Physiopathology and Clinical Implications
Filippos Triposkiadis[SUP] 1 [/SUP], Randall C Starling[SUP] 2 [/SUP], Andrew Xanthopoulos[SUP] 3 [/SUP], Javed Butler[SUP] 4 [/SUP], Harisios Boudoulas[SUP] 5 [/SUP]
Affiliations
- PMID: 33454213
- DOI: 10.1016/j.hlc.2020.11.008
Abstract
The severe acute respiratory syndrome coronavirus (SARS-CoV)-2, which is responsible for coronavirus disease 2019 (COVID-19), uses angiotensin (ANG)-converting enzyme 2 (ACE2) as the entrance receptor. Although most COVID-19 cases are mild, some are severe or critical, predominantly due to acute lung injury. It has been widely accepted that a counter regulatory renin-angiotensin system (RAS) axis including the ACE2/ANG [1-7]/Mas protects the lungs from acute lung injury. However, recent evidence suggests that the generation of protective ANG [1-7] in the lungs is predominantly mediated by proinflammatory prolyloligopeptidase (POP), which has been repeatedly demonstrated to be involved in lung pathology. This review contends that acute lung injury in severe COVID-19 is characterised by a) ACE2 downregulation and malfunction (inflammatory signalling) due to viral occupation, and b) dysregulation of the protective RAS axis, predominantly due to increased activity of proinflammatory POP. It follows that a reasonable treatment strategy in COVID-19-related acute lung injury would be delivering functional recombinant (r) ACE2 forms to trap the virus. Additionally, or alternatively to rACE2 delivery, the potential benefits resulting from lowering POP activity should also be explored. These treatment strategies deserve further investigation.
Keywords: Acute lung injury; Coronavirus disease 2019; Renin-angiotensin system.