Molecules in pathogenesis: angiotensin converting enzyme 2 (ACE2)

Wiese, Owen ; Zemlin, Annalise E. ; Pillay, Tahir S. (2021-04-19)

CITATION: Wiese, O.; Zemlin A. E. & Pillay, T. S. 2021. Molecules in pathogenesis: angiotensin converting enzyme 2 (ACE2). Journal of Clinical Pathology, 74:285-290. doi:10.1136/jclinpath-2020-206954

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The renin–angiotensin system is mainly associated with the regulation of blood pressure, but recently many other functions of this system have been described. ACE2, an 805-amino acid monocarboxypeptidase type I transmembrane glycoprotein, was discovered in 2000 and has sequence similarity to two other proteins, namely ACE and collectrin. The ACE2 gene is located on Xp22 and is highly polymorphic. ACE2 is expressed in numerous tissues especially the lung alveolar epithelial cells, heart, kidney and gastrointestinal tract. Animal studies have found that ACE2 is central in diseases affecting almost all organ systems, among other cardiac, respiratory, renal and endocrine functions. ACE2 was identified as the cellular contact point for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the cause of the global pandemic (COVID-19), and is a potential drug target. SARS-CoV-2 infection has several effects on the renin–angiotensin system and conversely, regulation of this receptor may affect the progress of infection. We describe the genetics and functions of ACE2, explore its various physiological functions in the renin–angiotensin system and discuss its role in the pathophysiology of disease. ACE2 opposes the vasopressor ACE pathway of the renin–angiotensin system by converting angiotensin (Ang) I to Ang (1–9) and Ang II to Ang (1–7) which initiates the vasodilatory pathway. ACE2 may have a protective effect in the lung and kidney as knockout mice display susceptibility to acute respiratory distress and hypertensive nephropathy. Binding of SARS-CoV-2 and the subsequent fusion and downregulation of this pathway during SARS-CoV-2 infection may explain some of the unusual sequelae seen in COVID-19. This article is made freely available for use in accordance with BMJ’s website terms and conditions for the duration of the covid-19 pandemic or until otherwise determined by BMJ. You may use, download and print the article for any lawful, non-commercial purpose (including text and data mining) provided that all copyright notices and trade marks are retained.

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