ACE2 Cell Biology, Regulation, and Physiological Functions

Angiotensin-converting enzyme 2 (ACE2), discovered as a homologue of ACE, acts as its physiological counterbalance providing homeostatic regulation of circulating angiotensin II (Ang II) levels. ACE2 is a zinc metalloenzyme and carboxypeptidase located as an ectoenzyme on the surface of endothelial and other cells. While its primary substrate appears to be Ang II, it can hydrolyze a number of other physiological substrates. Additionally, ACE2 functions in other noncatalytic cellular roles including the regulation of intestinal neutral amino acid transport. It also serendipitously acts as the receptor for the severe acute respiratory syndrome virus. Upregulation of ACE2 expression and function is increasingly recognized as a potential therapeutic strategy in hypertension and cardiovascular disease, diabetes, lung injury, and fibrotic disorders. ACE2 is regulated at multiple levels including transcriptional, posttranscriptional (miRNA and epigenetic), and posttranslational through its shedding from the cell surface.