ACE2 as therapeutic agent

• Published in: Clinical science (1979) Vol. 134; no. 19; p. 2581
• Main Authors: Li, Qiuhong, Grant, Maria B, Richards, Elaine M, Raizada, Mohan K
• Format: Journal Article
• Language: English
• Published: England 16-10-2020
• Subjects: Angiotensin-Converting Enzyme 2 - therapeutic use; Animals; Disease Models, Animal; Gene Transfer Techniques; Humans; Models, Biological; Organ Specificity; Renin-Angiotensin System; gene delivery; ACE2; Probiotics; Angiotensin II; Angiotensin-(1-7); renin-angiotensin system
• ISSN: 1470-8736
• DOI: 10.1042/CS20200570

The angiotensin-converting enzyme 2 (ACE2) has emerged as a critical regulator of the renin-angiotensin system (RAS), which plays important roles in cardiovascular homeostasis by regulating vascular tone, fluid and electrolyte balance. ACE2 functions as a carboxymonopeptidase hydrolyzing the cleavage of a single C-terminal residue from Angiotensin-II (Ang-II), the key peptide hormone of RAS, to form Angiotensin-(1-7) (Ang-(1-7)), which binds to the G-protein-coupled Mas receptor and activates signaling pathways that counteract the pathways activated by Ang-II. ACE2 is expressed in a variety of tissues and overwhelming evidence substantiates the beneficial effects of enhancing ACE2/Ang-(1-7)/Mas axis under many pathological conditions in these tissues in experimental models. This review will provide a succinct overview on current strategies to enhance ACE2 as therapeutic agent, and discuss limitations and future challenges. ACE2 also has other functions, such as acting as a co-factor for amino acid transport and being exploited by the severe acute respiratory syndrome coronaviruses (SARS-CoVs) as cellular entry receptor, the implications of these functions in development of ACE2-based therapeutics will also be discussed.