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Article: Adipocyte fatty acid-binding protein exacerbates cerebral ischemia injury by disrupting the blood-brain barrier

TitleAdipocyte fatty acid-binding protein exacerbates cerebral ischemia injury by disrupting the blood-brain barrier
Authors
KeywordsA-FABP
Blood–brain barrier
Ischaemic stroke
JNK/c-Jun signalling
MMP-9
Issue Date2020
PublisherOxford University Press. The Journal's web site is located at http://eurheartj.oxfordjournals.org/
Citation
European Heart Journal, 2020, Epub 2020-04-29 How to Cite?
AbstractAims: Adipocyte fatty acid-binding protein (A-FABP) is an adipokine implicating in various metabolic diseases. Elevated circulating levels of A-FABP correlate positively with poor prognosis in ischaemic stroke (IS) patients. No information is available concerning the role of A-FABP in the pathogenesis of IS. Experiments were designed to determine whether or not A-FABP mediates blood–brain barrier (BBB) disruption, and if so, to explore the molecular mechanisms underlying this deleterious effects. Methods and results: Circulating A-FABP and its cerebral expression were increased in mice after middle cerebral artery occlusion. Genetic deletion and pharmacological inhibition of A-FABP alleviated cerebral ischaemia injury with reduced infarction volume, cerebral oedema, neurological deficits, and neuronal apoptosis; BBB disruption was attenuated and accompanied by reduced degradation of tight junction proteins and induction of matrix metalloproteinases-9 (MMP-9). In patients with acute IS, elevated circulating A-FABP levels positively correlated with those of MMP-9 and cerebral infarct volume. Mechanistically, ischaemia-induced elevation of A-FABP selectively in peripheral blood monocyte-derived macrophages and cerebral resident microglia promoted MMP-9 transactivation by potentiating JNK/c-Jun signalling, enhancing degradation of tight junction proteins and BBB leakage. The detrimental effects of A-FABP were prevented by pharmacological inhibition of MMP-9. Conclusion: A-FABP is a key mediator of cerebral ischaemia injury promoting MMP-9-mediated BBB disruption. Inhibition of A-FABP is a potential strategy to improve IS outcome.
Persistent Identifierhttp://hdl.handle.net/10722/282207
ISSN
2019 Impact Factor: 22.673
2015 SCImago Journal Rankings: 6.997

 

DC FieldValueLanguage
dc.contributor.authorLiao, B-
dc.contributor.authorGeng, L-
dc.contributor.authorZhang, F-
dc.contributor.authorShu, L-
dc.contributor.authorWei, L-
dc.contributor.authorYeung, PKK-
dc.contributor.authorLam, KSL-
dc.contributor.authorChung, SK-
dc.contributor.authorChang, J-
dc.contributor.authorVanhoutte, PM-
dc.contributor.authorXu, A-
dc.contributor.authorWang, K-
dc.contributor.authorHoo, RLC-
dc.date.accessioned2020-05-05T14:32:10Z-
dc.date.available2020-05-05T14:32:10Z-
dc.date.issued2020-
dc.identifier.citationEuropean Heart Journal, 2020, Epub 2020-04-29-
dc.identifier.issn0195-668X-
dc.identifier.urihttp://hdl.handle.net/10722/282207-
dc.description.abstractAims: Adipocyte fatty acid-binding protein (A-FABP) is an adipokine implicating in various metabolic diseases. Elevated circulating levels of A-FABP correlate positively with poor prognosis in ischaemic stroke (IS) patients. No information is available concerning the role of A-FABP in the pathogenesis of IS. Experiments were designed to determine whether or not A-FABP mediates blood–brain barrier (BBB) disruption, and if so, to explore the molecular mechanisms underlying this deleterious effects. Methods and results: Circulating A-FABP and its cerebral expression were increased in mice after middle cerebral artery occlusion. Genetic deletion and pharmacological inhibition of A-FABP alleviated cerebral ischaemia injury with reduced infarction volume, cerebral oedema, neurological deficits, and neuronal apoptosis; BBB disruption was attenuated and accompanied by reduced degradation of tight junction proteins and induction of matrix metalloproteinases-9 (MMP-9). In patients with acute IS, elevated circulating A-FABP levels positively correlated with those of MMP-9 and cerebral infarct volume. Mechanistically, ischaemia-induced elevation of A-FABP selectively in peripheral blood monocyte-derived macrophages and cerebral resident microglia promoted MMP-9 transactivation by potentiating JNK/c-Jun signalling, enhancing degradation of tight junction proteins and BBB leakage. The detrimental effects of A-FABP were prevented by pharmacological inhibition of MMP-9. Conclusion: A-FABP is a key mediator of cerebral ischaemia injury promoting MMP-9-mediated BBB disruption. Inhibition of A-FABP is a potential strategy to improve IS outcome.-
dc.languageeng-
dc.publisherOxford University Press. The Journal's web site is located at http://eurheartj.oxfordjournals.org/-
dc.relation.ispartofEuropean Heart Journal-
dc.rightsThis work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.-
dc.subjectA-FABP-
dc.subjectBlood–brain barrier-
dc.subjectIschaemic stroke-
dc.subjectJNK/c-Jun signalling-
dc.subjectMMP-9-
dc.titleAdipocyte fatty acid-binding protein exacerbates cerebral ischemia injury by disrupting the blood-brain barrier-
dc.typeArticle-
dc.identifier.emailLiao, B: babylia@hku.hk-
dc.identifier.emailGeng, L: u3003135@hku.hk-
dc.identifier.emailShu, L: shinyshu@hku.hk-
dc.identifier.emailLam, KSL: ksllam@hku.hk-
dc.identifier.emailVanhoutte, PM: vanhoutt@hku.hk-
dc.identifier.emailXu, A: amxu@hkucc.hku.hk-
dc.identifier.emailHoo, RLC: rubyhoo@hkucc.hku.hk-
dc.identifier.authorityLam, KSL=rp00343-
dc.identifier.authorityChung, SK=rp00381-
dc.identifier.authorityVanhoutte, PM=rp00238-
dc.identifier.authorityXu, A=rp00485-
dc.identifier.authorityHoo, RLC=rp01334-
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.1093/eurheartj/ehaa207-
dc.identifier.pmid32350521-
dc.identifier.hkuros309835-
dc.identifier.volumeEpub 2020-04-29-
dc.publisher.placeUnited Kingdom-

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