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dc.contributor.author
Doytcheva, Petia
dc.contributor.author
Bächler, Thomas
dc.contributor.author
Tarasco, Erika
dc.contributor.author
Marzolla, Vincenzo
dc.contributor.author
Engeli, Michael
dc.contributor.author
Pellegrini, Giovanni
dc.contributor.author
Stivala, Simona
dc.contributor.author
Rohrer, Lucia
dc.contributor.author
Tona, Francesco
dc.contributor.author
Camici, Giovanni G.
dc.contributor.author
Vanhoutte, Paul M.
dc.contributor.author
Matter, Christian M.
dc.contributor.author
Lutz, Thomas A.
dc.contributor.author
Lüscher, Thomas F.
dc.contributor.author
Osto, Elena
dc.date.accessioned
2017-12-11T13:21:20Z
dc.date.available
2017-12-05T05:43:29Z
dc.date.available
2017-12-11T13:21:20Z
dc.date.issued
2017-11
dc.identifier.other
10.1161/JAHA.117.006441
en_US
dc.identifier.uri
http://hdl.handle.net/20.500.11850/217095
dc.identifier.doi
10.3929/ethz-b-000217095
dc.description.abstract
Background Roux‐en‐Y gastric bypass (RYGB) reduces obesity‐associated comorbidities and cardiovascular mortality. RYGB improves endothelial dysfunction, reducing c‐Jun N‐terminal kinase (JNK) vascular phosphorylation. JNK activation links obesity with insulin resistance and endothelial dysfunction. Herein, we examined whether JNK1 or JNK2 mediates obesity‐induced endothelial dysfunction and if pharmacological JNK inhibition can mimic RYGB vascular benefits. Methods and Results After 7 weeks of a high‐fat high‐cholesterol diet, obese rats underwent RYGB or sham surgery; sham–operated ad libitum–fed rats received, for 8 days, either the control peptide D‐TAT or the JNK peptide inhibitor D‐JNKi‐1 (20 mg/kg per day subcutaneous). JNK peptide inhibitor D‐JNKi‐1 treatment improved endothelial vasorelaxation in response to insulin and glucagon‐like peptide‐1, as observed after RYGB. Obesity increased aortic phosphorylation of JNK2, but not of JNK1. RYGB and JNK peptide inhibitor D‐JNKi‐1 treatment blunted aortic JNK2 phosphorylation via activation of glucagon‐like peptide‐1–mediated signaling. The inhibitory phosphorylation of insulin receptor substrate‐1 was reduced, whereas the protein kinase B/endothelial NO synthase pathway was increased and oxidative stress was decreased, resulting in improved vascular NO bioavailability. Conclusions Decreased aortic JNK2 phosphorylation after RYGB rapidly improves obesity‐induced endothelial dysfunction. Pharmacological JNK inhibition mimics the endothelial protective effects of RYGB. These findings highlight the therapeutic potential of novel strategies targeting vascular JNK2 against the severe cardiovascular disease associated with obesity.
en_US
dc.language.iso
en
en_US
dc.publisher
American Heart Association
en_US
dc.rights.uri
http://creativecommons.org/licenses/by-nc-nd/4.0/
dc.subject
Bariatric surgery
en_US
dc.subject
c-Jun N-terminal kinase
en_US
dc.subject
Endothelial function
en_US
dc.subject
Glucagon-like peptide-1
en_US
dc.subject
NO
en_US
dc.subject
obesity
en_US
dc.title
Inhibition of vascular c-jun N-terminal kinase 2 improves obesity-induced endothelial dysfunction after roux-en-y gastric bypass
en_US
dc.type
Journal Article
dc.rights.license
Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International
dc.date.published
2017-11-14
ethz.journal.title
Journal of the American Heart Association
ethz.journal.volume
6
en_US
ethz.journal.issue
11
en_US
ethz.pages.start
e006441
en_US
ethz.size
27 p.
en_US
ethz.version.deposit
publishedVersion
en_US
ethz.identifier.scopus
ethz.publication.place
New York, NY
en_US
ethz.publication.status
published
en_US
ethz.date.deposited
2017-12-05T05:43:31Z
ethz.source
SCOPUS
ethz.eth
yes
en_US
ethz.availability
Open access
en_US
ethz.rosetta.installDate
2017-12-11T13:21:23Z
ethz.rosetta.lastUpdated
2017-12-11T13:21:23Z
ethz.rosetta.versionExported
true
ethz.COinS
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