Open AccessAngiotensin Converting Enzyme 2/Ang‐(1–7)/Mas Axis Protects Brain from Ischemic Injury with a Tendency of Age‐dependence
Author(s) -
Zheng JiaoLin,
Li GuangZe,
Chen ShuZhen,
Wang JinJu,
Olson James E.,
Xia HuiJing,
Lazartigues Eric,
Zhu YuLan,
Chen YanFang
Publication year - 2014
Publication title -
cns neuroscience and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.403
H-Index - 69
eISSN - 1755-5949
pISSN - 1755-5930
DOI - 10.1111/cns.12233
Subject(s) - angiotensin converting enzyme 2 , nox4 , medicine , agonist , renin–angiotensin system , ischemia , brain ischemia , reactive oxygen species , angiotensin converting enzyme , pharmacology , stroke (engine) , receptor , endocrinology , anesthesia , chemistry , nadph oxidase , oxidative stress , biochemistry , mechanical engineering , disease , covid-19 , blood pressure , infectious disease (medical specialty) , engineering
Summary Background The angiotensin (Ang) converting enzyme 2 ( ACE 2)/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. Aims This study explored whether the ACE 2/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 ACE 2 ( 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.