title: Neuroprotective mechanisms of the ACE2-angiotensin-(1-7)-Mas axis in stroke.
abstract: The discovery of beneficial neuroprotective effects of the angiotensin converting enzyme 2-angiotensin-(1-7)-Mas axis [ACE2-Ang-(1-7)-Mas] in ischemic and hemorrhagic stroke has spurred interest in a more complete characterization of its mechanisms of action. Here, we summarize findings that describe the protective role of the ACE2-Ang-(1-7)-Mas axis in stroke, along with a focused discussion on the potential mechanisms of neuroprotective effects of Ang-(1-7) in stroke. The latter incorporates evidence describing the actions of Ang-(1-7) to counter the deleterious effects of angiotensin II (AngII) via its type 1 receptor, including anti-inflammatory, anti-oxidant, vasodilatory, and angiogenic effects, and the role of altered kinase-phosphatase signaling. Interactions of Mas with other receptors, including bradykinin receptors and AngII type 2 receptors are also considered. A more complete understanding of the mechanisms of action of Ang-(1-7) to elicit neuroprotection will serve as an essential step toward research into potential targeted therapeutics in the clinical setting.
authors.affiliation: Department of Physiology and Functional Genomics & McKnight Brain Institute, University of Florida, 1600 SW Archer Road, PO Box 100274, Gainesville, FL, 32610-0274, USA, douglasbennion@ufl.edu.
authors.forename: Douglas M
authors.initials: DM
authors.lastname: Bennion
authors.forename: Emily
authors.initials: E
authors.lastname: Haltigan
authors.forename: Robert W
authors.initials: RW
authors.lastname: Regenhardt
authors.forename: U Muscha
authors.initials: UM
authors.lastname: Steckelings
authors.forename: Colin
authors.initials: C
authors.lastname: Sumners
mesh_terms: D000803:Angiotensin I / Q000378:metabolism*; D000085962:Angiotensin-Converting Enzyme 2; D000818:Animals; D006801:Humans; D018696:Neuroprotective Agents / Q000494:pharmacology; D010446:Peptide Fragments / Q000378:metabolism*; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D020521:Stroke / Q000378:metabolism*
chemical_list: D018696:Neuroprotective Agents; D010446:Peptide Fragments; D000803:Angiotensin I; D007703:Peptidyl-Dipeptidase A; C000705307:ACE2 protein, human; D000085962:Angiotensin-Converting Enzyme 2; C118790:angiotensin I (1-7)