Assessing the effects of Ang-(1-7) therapy following transient middle cerebral artery occlusion

Arroja, M.M.C., Reid, E. , Roy, L.A., Vallatos, A.V. , Holmes, W.M. , Nicklin, S.A. , Work, L.M. and McCabe, C. (2019) Assessing the effects of Ang-(1-7) therapy following transient middle cerebral artery occlusion. Scientific Reports, 9, 3154. (doi: 10.1038/s41598-019-39102-8) (PMID:30816157) (PMCID:PMC6395816)

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The counter-regulatory axis, Angiotensin Converting Enzyme 2, Angiotensin-(1-7), Mas receptor (ACE2/Ang-1-7/MasR), of the renin angiotensin system (RAS) is a potential therapeutic target in stroke, with Ang-(1-7) reported to have neuroprotective effects in pre-clinical stroke models. Here, an extensive investigation of the functional and mechanistic effects of Ang-(1-7) was performed in a rodent model of stroke. Using longitudinal magnetic resonance imaging (MRI) it was observed that central administration of Ang-(1-7) following transient middle cerebral artery occlusion (MCAO) increased the amount of tissue salvage compared to reperfusion alone. This protective effect was not due to early changes in blood brain barrier (BBB) permeability, microglia activation or inflammatory gene expression. However, increases in NADPH oxidase 1 (Nox1) mRNA expression were observed in the treatment group compared to control. In order to determine whether Ang-(1-7) has direct cerebrovascular effects, laser speckle contrast imaging (LSCI) was performed to measure dynamic changes in cortical perfusion following reperfusion. Delivery of Ang-(1-7) did not have any effect on cortical perfusion following reperfusion however; it showed an indication to prevent the ‘steal phenomenon’ within the contralateral hemisphere. The comprehensive series of studies have demonstrated a moderate protective effect of Ang-(1-7) when given alongside reperfusion to increase tissue salvage.

Item Type:Articles
Glasgow Author(s) Enlighten ID:Nicklin, Professor Stuart and McCabe, Dr Chris and Holmes, Dr William and Work, Dr Lorraine and Reid, Dr Emma and Vallatos, Dr Antoine and Arroja, Mariana Moreira Coutinho
Authors: Arroja, M.M.C., Reid, E., Roy, L.A., Vallatos, A.V., Holmes, W.M., Nicklin, S.A., Work, L.M., and McCabe, C.
College/School:College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health
College of Medical Veterinary and Life Sciences > School of Psychology & Neuroscience
College of Medical Veterinary and Life Sciences > School of Life Sciences
Journal Name:Scientific Reports
Publisher:Nature Research
ISSN (Online):2045-2322
Copyright Holders:Copyright © 2019 The Authors
First Published:First published in Scientific Reports 9:3154
Publisher Policy:Reproduced under a Creative Commons License

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
632341MRC Doctoral Training Grant 2013/14, 2014/15 and 2015/16George BaillieMedical Research Council (MRC)MR/K501335/1MVLS GRADUATE SCHOOL