ACE2: a new target for cardiovascular disease therapeutics.
The discovery of angiotensin-converting enzyme 2 (ACE2) in 2000 is an important event in the renin-angiotensin system (RAS) story. This enzyme, an homolog of ACE, hydrolyzes angiotensin (Ang) I to produce Ang-(1-9), which is subsequently converted into Ang-(1-7) by a neutral endopeptidase and ACE. ACE2 releases Ang-(1-7) more efficiently than its catalysis of Ang-(1-9) by cleavage of Pro(7)-Phe(8) bound in Ang II. Thus, the major biologically active product of ACE2 is Ang-(1-7), which is considered to be a beneficial peptide of the RAS cascade in the cardiovascular system. This enzyme has 42% identity with the catalytic domain of ACE, is present in most cardiovascular-relevant tissues, and is an ectoenzyme as ACE. Despite these similarities, ACE2 is distinct from ACE. Since it is a monocarboxypeptidase, it has only 1 catalytic site and is insensitive to ACE inhibitors. As a result, ACE2 is a central enzyme in balancing vasoconstrictor and proliferative actions of Ang II with vasodilatory and antiproliferative effects of Ang-(1-7). In this review, we will summarize the role of ACE2 in the cardiovascular system and discuss the importance of ACE2-Ang-(1-7) axis in the control of normal cardiovascular physiology and ACE2 as a potential target in the development of novel therapeutic agents for cardiovascular diseases.
Raizada
Mohan K
MK
Department of Physiology and Functional Genomics, College of Medicine, University of Florida, Gainesville, Florida 32610, USA. mraizada@phys.med.ufl.edu
Ferreira
Anderson J
AJ
D000803:Angiotensin I / Q000502:physiology; D000085962:Angiotensin-Converting Enzyme 2; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D002318:Cardiovascular Diseases / Q000188:drug therapy* / Q000503:physiopathology; D002320:Cardiovascular Physiological Phenomena; D016503:Drug Delivery Systems; D006801:Humans; D010446:Peptide Fragments / Q000502:physiology; D007703:Peptidyl-Dipeptidase A / Q000187:drug effects*; D012084:Renin-Angiotensin System / Q000502:physiology; D015398:Signal Transduction
D000806:Angiotensin-Converting Enzyme Inhibitors; D010446:Peptide Fragments; D000803:Angiotensin I; D007703:Peptidyl-Dipeptidase A; C000705307:ACE2 protein, human; D000085962:Angiotensin-Converting Enzyme 2; C118790:angiotensin I (1-7)