title: Angiotensin converting enzyme 2/Ang-(1-7)/mas axis protects brain from ischemic injury with a tendency of age-dependence.
abstract: BACKGROUND
  The angiotensin (Ang) converting enzyme 2 (ACE2)/Ang-(1-7)/Mas receptor pathway is an important component of the renin-angiotensin system and has been suggested to exert beneficial effects in ischemic stroke.
  
  
  OBJECTIVE
  This study explored whether the ACE2/Ang-(1-7)/Mas pathway has a protective effect on cerebral ischemic injury and whether this effect is affected by age.
  
  
  METHODS
  We used three-month and eight-month transgenic mice with neural over-expression of ACE2 (SA) and their age-matched nontransgenic (NT) controls. Neurological deficits and ischemic stroke volume were determined following middle cerebral artery occlusion (MCAO). In oxygen and glucose deprivation (OGD) experiments on brain slices, the effects of the Mas receptor agonist (Ang1-7) or antagonist (A779) on tissue swelling, Nox2/Nox4 expression reactive oxygen species (ROS) production and cell death were measured.
  
  
  RESULTS
  (1) Middle cerebral artery occlusion -induced ischemic injury and neurological deficit were reduced in SA mice, especially in eight-month animals; (2) OGD-induced tissue swelling and cell death were decreased in SA mice with a greater reduction seen in eight-month mice; (3) Ang-(1-7) and A779 had opposite effects on OGD-induced responses, which correlated with changes in Nox2/Nox4 expression and ROS production.
  
  
  CONCLUSIONS
  Angiotensin converting enzyme 2/Ang-(1-7)/Mas axis protects brain from ischemic injury via the Nox/ROS signaling pathway, with a greater effect in older animals.
authors.affiliation: Department of Pharmacology and Toxicology, Wright State University Boonshoft School of Medicine, Dayton, OH, USA; Department of Neurology, the Second Hospital of Harbin Medical University, Harbin, China.
authors.forename: Jiao-Lin
authors.initials: JL
authors.lastname: Zheng
authors.forename: Guang-Ze
authors.initials: GZ
authors.lastname: Li
authors.forename: Shu-Zhen
authors.initials: SZ
authors.lastname: Chen
authors.forename: Jin-Ju
authors.initials: JJ
authors.lastname: Wang
authors.forename: James E
authors.initials: JE
authors.lastname: Olson
authors.forename: Hui-Jing
authors.initials: HJ
authors.lastname: Xia
authors.forename: Eric
authors.initials: E
authors.lastname: Lazartigues
authors.forename: Yu-Lan
authors.initials: YL
authors.lastname: Zhu
authors.forename: Yan-Fang
authors.initials: YF
authors.lastname: Chen
mesh_terms: D000367:Age Factors; D000803:Angiotensin I / Q000378:metabolism*; D000804:Angiotensin II / Q000031:analogs & derivatives* / Q000378:metabolism; D000085962:Angiotensin-Converting Enzyme 2; D000818:Animals; D001921:Brain / Q000473:pathology / Q000503:physiopathology*; D001929:Brain Edema / Q000209:etiology / Q000473:pathology / Q000503:physiopathology; D002545:Brain Ischemia / Q000209:etiology / Q000473:pathology / Q000503:physiopathology*; D016923:Cell Death / Q000502:physiology; D005260:Female; D005947:Glucose / Q000172:deficiency; D002534:Hypoxia, Brain / Q000473:pathology / Q000503:physiopathology; D020244:Infarction, Middle Cerebral Artery / Q000150:complications / Q000473:pathology / Q000503:physiopathology; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism; D008822:Mice, Transgenic; D000074662:NADPH Oxidase 2; D000074663:NADPH Oxidase 4; D019255:NADPH Oxidases / Q000378:metabolism; D009474:Neurons / Q000473:pathology / Q000502:physiology*; D010446:Peptide Fragments / Q000378:metabolism*; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism; D020521:Stroke / Q000209:etiology / Q000473:pathology / Q000503:physiopathology; D046509:Tissue Culture Techniques
chemical_list: C092006:7-Ala-angiotensin (1-7); D008562:Membrane Glycoproteins; D010446:Peptide Fragments; D017382:Reactive Oxygen Species; D000804:Angiotensin II; D000803:Angiotensin I; C488842:Cybb protein, mouse; D000074662:NADPH Oxidase 2; D000074663:NADPH Oxidase 4; D019255:NADPH Oxidases; C422943:Nox4 protein, mouse; D007703:Peptidyl-Dipeptidase A; C000705328:Ace2 protein, mouse; D000085962:Angiotensin-Converting Enzyme 2; C118790:angiotensin I (1-7); D005947:Glucose
keywords: Aging; Angiotensin; Angiotensin-converting enzyme 2; Ischemic stroke; NADPH oxidase