title: Intracrine angiotensin II functions originate from noncanonical pathways in the human heart.
abstract: Although it is well-known that excess renin angiotensin system (RAS) activity contributes to the pathophysiology of cardiac and vascular disease, tissue-based expression of RAS genes has given rise to the possibility that intracellularly produced angiotensin II (Ang II) may be a critical contributor to disease processes. An extended form of angiotensin I (Ang I), the dodecapeptide angiotensin-(1-12) [Ang-(1-12)], that generates Ang II directly from chymase, particularly in the human heart, reinforces the possibility that an alternative noncanonical renin independent pathway for Ang II formation may be important in explaining the mechanisms by which the hormone contributes to adverse cardiac and vascular remodeling. This review summarizes the work that has been done in evaluating the functional significance of Ang-(1-12) and how this substrate generated from angiotensinogen by a yet to be identified enzyme enhances knowledge about Ang II pathological actions.
authors.affiliation: Departments of Surgery, Internal Medicine-Nephrology and Physiology-Pharmacology, Wake Forest University Health Science Center, Winston-Salem, North Carolina; cferrari@wakehealth.edu.
authors.forename: Carlos M
authors.initials: CM
authors.lastname: Ferrario
authors.affiliation: Departments of Surgery, Internal Medicine-Nephrology and Physiology-Pharmacology, Wake Forest University Health Science Center, Winston-Salem, North Carolina;
authors.forename: Sarfaraz
authors.initials: S
authors.lastname: Ahmad
authors.affiliation: Departments of Surgery, Internal Medicine-Nephrology and Physiology-Pharmacology, Wake Forest University Health Science Center, Winston-Salem, North Carolina; Hypertension and Vascular Research Center, Wake Forest University Health Science Center, Winston-Salem, North Carolina;
authors.forename: Jasmina
authors.initials: J
authors.lastname: Varagic
authors.affiliation: Section on Cardiovascular Medicine, Department of Internal Medicine, Wake Forest University Health Science Center, Winston-Salem, North Carolina;
authors.forename: Che Ping
authors.initials: CP
authors.lastname: Cheng
authors.affiliation: Hypertension and Vascular Research Center, Wake Forest University Health Science Center, Winston-Salem, North Carolina; Department of Anesthesiology, Wake Forest University Health Science Center, Winston-Salem, North Carolina;
authors.forename: Leanne
authors.initials: L
authors.lastname: Groban
authors.affiliation: Department of Anesthesiology, Wake Forest University Health Science Center, Winston-Salem, North Carolina;
authors.forename: Hao
authors.initials: H
authors.lastname: Wang
authors.affiliation: Departments of Cell Biology, Microbiology, Physiology, University of Alabama Birmingham, Alabama; and.
authors.forename: James F
authors.initials: JF
authors.lastname: Collawn
authors.affiliation: Departments of Cell Biology, Microbiology, Physiology, University of Alabama Birmingham, Alabama; and Division of Cardiovascular Disease, University of Alabama at Birmingham and Department of Veterans Affairs, Birmingham Veterans Affairs Medical Center, Birmingham, Alabama.
authors.forename: Louis J
authors.initials: LJ
authors.lastname: Dell Italia
mesh_terms: D000804:Angiotensin II / Q000378:metabolism*; D000808:Angiotensinogen / Q000378:metabolism*; D000818:Animals; D053818:Chymases; D006321:Heart / Q000503:physiopathology*; D006801:Humans; D009206:Myocardium / Q000378:metabolism*; D010446:Peptide Fragments / Q000378:metabolism*; D012084:Renin-Angiotensin System; D066253:Vascular Remodeling / Q000502:physiology; D020257:Ventricular Remodeling / Q000502:physiology
chemical_list: D010446:Peptide Fragments; C000610416:angiotensin-(1-12), human; D000808:Angiotensinogen; D000804:Angiotensin II; D053818:Chymases
keywords: angiotensin-(1–12), angiotensin converting enzyme inhibitors; heart chymase; heart failure; hypertension