Advances in biochemical and functional roles of angiotensin-converting enzyme 2 and angiotensin-(1-7) in regulation of cardiovascular function.
Angiotensin-converting enzyme 2 (ACE2) is the first human homologue of ACE to be described. ACE2 is a type I integral membrane protein that functions as a carboxypeptidase, cleaving a single hydrophobic/basic residue from the COOH-terminus of its substrates. Because ACE2 efficiently hydrolyzes the potent vasoconstrictor angiotensin II to angiotensin (1-7), this has changed our overall perspective about the classical view of the renin angiotensin system in the regulation of hypertension and heart and renal function, because it represents the first example of a feedforward mechanism directed toward mitigation of the actions of angiotensin II. This paper reviews the new data regarding the biochemistry of angiotensin-(1-7)-forming enzymes and discusses key findings such as the elucidation of the regulatory mechanisms participating in the expression of ACE2 and angiotensin-(1-7) in the control of the circulation.
Ferrario
Carlos M
CM
Hypertension and Vascular Disease Center, Wake Forest Univ. School of Medicine, Winston-Salem, NC 27157, USA. cferrari@wfubmc.edu
Trask
Aaron J
AJ
Jessup
Jewell A
JA
D000803:Angiotensin I / Q000378:metabolism*; D000085962:Angiotensin-Converting Enzyme 2; D000818:Animals; D001671:Biochemistry / Q000639:trends*; D001794:Blood Pressure; D002268:Carboxypeptidases / Q000378:metabolism*; D002319:Cardiovascular System / Q000503:physiopathology*; D005246:Feedback; D006801:Humans; D006973:Hypertension / Q000503:physiopathology*; D009203:Myocardial Infarction / Q000503:physiopathology; D010446:Peptide Fragments / Q000378:metabolism*; D007703:Peptidyl-Dipeptidase A; D012084:Renin-Angiotensin System
D010446:Peptide Fragments; D000803:Angiotensin I; D002268:Carboxypeptidases; D007703:Peptidyl-Dipeptidase A; C000705307:ACE2 protein, human; D000085962:Angiotensin-Converting Enzyme 2; C118790:angiotensin I (1-7)