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Article: Uncoupling protein-2 protects endothelial function in diet-induced obese mice

TitleUncoupling protein-2 protects endothelial function in diet-induced obese mice
Authors
Issue Date2012
PublisherLippincott Williams & Wilkins. The Journal's web site is located at http://circres.ahajournals.org
Citation
Circulation Research, 2012, v. 110 n. 9, p. 1211-1216 How to Cite?
AbstractRationale: Previous studies indicate uncoupling protein-2 (UCP2) as an antioxidant defense against endothelial dysfunction in hypertension. UCP2 also regulates insulin secretion and action. However, the role of UCP2 in endothelial dysfunction associated with diabetes and obesity is unclear. Objective: UCP2 protects against endothelial dysfunction induced by high-fat diet through inhibition of reactive oxygen species (ROS) production, and subsequent increase of nitric oxide bioavailability. Methods and Results: Endothelium-dependent relaxation (EDR) in aortae and mesenteric arteries in response to acetylcholine was measured in wire myograph. Flow-mediated vasodilatation in 2-order mesenteric arteries was measured in pressure myograph. ROS production is measured by CM-H2DCFDA and DHE fluorescence. High-glucose exposure reduced EDR in mouse aortae, which was exaggerated in UCP2 knockout (KO) mice, whereas UCP2 overexpression by adenoviral infection (AdUCP2) restored the impaired EDR. Impairment of EDR and flow-mediated vasodilatation in aortae and mesenteric arteries from high-fat diet-induced obese mice (DIO) was exaggerated in UCP2KO DIO mice compared with wild-type DIO littermates, whereas AdUCP2 i.v. injection restored both EDR and flow-mediated vasodilatation in DIO mice. Improved EDR in mesenteric arteries was inhibited by nitric oxide synthase inhibitor. UCP2 overexpression also inhibited intracellular ROS production in the en face endothelium of aorta and mesenteric artery of DIO mice, whereas UCP2 deficiency enhanced ROS production. Conclusions: UCP2 preserves endothelial function through increasing nitric oxide bioavailability secondary to the inhibition of ROS production in the endothelium of obese diabetic mice. © 2012 American Heart Association, Inc.
Persistent Identifierhttp://hdl.handle.net/10722/163487
ISSN
2015 Impact Factor: 11.551
2015 SCImago Journal Rankings: 5.755
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorTian, XYen_US
dc.contributor.authorWong, WTen_US
dc.contributor.authorXu, Aen_US
dc.contributor.authorLu, Yen_US
dc.contributor.authorZhang, Yen_US
dc.contributor.authorWang, Len_US
dc.contributor.authorCheang, WSen_US
dc.contributor.authorWang, Yen_US
dc.contributor.authorYao, Xen_US
dc.contributor.authorHuang, Yen_US
dc.date.accessioned2012-09-05T05:32:01Z-
dc.date.available2012-09-05T05:32:01Z-
dc.date.issued2012en_US
dc.identifier.citationCirculation Research, 2012, v. 110 n. 9, p. 1211-1216en_US
dc.identifier.issn0009-7330en_US
dc.identifier.urihttp://hdl.handle.net/10722/163487-
dc.description.abstractRationale: Previous studies indicate uncoupling protein-2 (UCP2) as an antioxidant defense against endothelial dysfunction in hypertension. UCP2 also regulates insulin secretion and action. However, the role of UCP2 in endothelial dysfunction associated with diabetes and obesity is unclear. Objective: UCP2 protects against endothelial dysfunction induced by high-fat diet through inhibition of reactive oxygen species (ROS) production, and subsequent increase of nitric oxide bioavailability. Methods and Results: Endothelium-dependent relaxation (EDR) in aortae and mesenteric arteries in response to acetylcholine was measured in wire myograph. Flow-mediated vasodilatation in 2-order mesenteric arteries was measured in pressure myograph. ROS production is measured by CM-H2DCFDA and DHE fluorescence. High-glucose exposure reduced EDR in mouse aortae, which was exaggerated in UCP2 knockout (KO) mice, whereas UCP2 overexpression by adenoviral infection (AdUCP2) restored the impaired EDR. Impairment of EDR and flow-mediated vasodilatation in aortae and mesenteric arteries from high-fat diet-induced obese mice (DIO) was exaggerated in UCP2KO DIO mice compared with wild-type DIO littermates, whereas AdUCP2 i.v. injection restored both EDR and flow-mediated vasodilatation in DIO mice. Improved EDR in mesenteric arteries was inhibited by nitric oxide synthase inhibitor. UCP2 overexpression also inhibited intracellular ROS production in the en face endothelium of aorta and mesenteric artery of DIO mice, whereas UCP2 deficiency enhanced ROS production. Conclusions: UCP2 preserves endothelial function through increasing nitric oxide bioavailability secondary to the inhibition of ROS production in the endothelium of obese diabetic mice. © 2012 American Heart Association, Inc.en_US
dc.languageengen_US
dc.publisherLippincott Williams & Wilkins. The Journal's web site is located at http://circres.ahajournals.orgen_US
dc.relation.ispartofCirculation Researchen_US
dc.subject.meshAnimalsen_US
dc.subject.meshAorta, Thoracic - Drug Effects - Metabolism - Physiopathologyen_US
dc.subject.meshDiet, High-Faten_US
dc.subject.meshDisease Models, Animalen_US
dc.subject.meshDose-Response Relationship, Drugen_US
dc.subject.meshEndothelium, Vascular - Drug Effects - Metabolism - Physiopathologyen_US
dc.subject.meshEnzyme Inhibitors - Pharmacologyen_US
dc.subject.meshFree Radical Scavengers - Pharmacologyen_US
dc.subject.meshGlucose - Metabolismen_US
dc.subject.meshHuman Umbilical Vein Endothelial Cells - Metabolismen_US
dc.subject.meshHumansen_US
dc.subject.meshIon Channels - Deficiency - Genetics - Metabolismen_US
dc.subject.meshMaleen_US
dc.subject.meshMesenteric Arteries - Drug Effects - Metabolism - Physiopathologyen_US
dc.subject.meshMiceen_US
dc.subject.meshMice, Inbred C57blen_US
dc.subject.meshMice, Knockouten_US
dc.subject.meshMitochondrial Proteins - Deficiency - Genetics - Metabolismen_US
dc.subject.meshMyographyen_US
dc.subject.meshNitric Oxide - Metabolismen_US
dc.subject.meshNitric Oxide Synthase - Antagonists & Inhibitors - Metabolismen_US
dc.subject.meshObesity - Etiology - Metabolism - Physiopathologyen_US
dc.subject.meshOrgan Culture Techniquesen_US
dc.subject.meshOxidative Stressen_US
dc.subject.meshReactive Oxygen Species - Metabolismen_US
dc.subject.meshRegional Blood Flowen_US
dc.subject.meshTime Factorsen_US
dc.subject.meshTransfectionen_US
dc.subject.meshVasodilation - Drug Effectsen_US
dc.subject.meshVasodilator Agents - Pharmacologyen_US
dc.titleUncoupling protein-2 protects endothelial function in diet-induced obese miceen_US
dc.typeArticleen_US
dc.identifier.emailXu, A:amxu@hkucc.hku.hken_US
dc.identifier.authorityXu, A=rp00485en_US
dc.description.naturelink_to_subscribed_fulltexten_US
dc.identifier.doi10.1161/CIRCRESAHA.111.262170en_US
dc.identifier.pmid22461387en_US
dc.identifier.scopuseid_2-s2.0-84860758607en_US
dc.identifier.hkuros205684-
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-84860758607&selection=ref&src=s&origin=recordpageen_US
dc.identifier.volume110en_US
dc.identifier.issue9en_US
dc.identifier.spage1211en_US
dc.identifier.epage1216en_US
dc.identifier.isiWOS:000303406200016-
dc.publisher.placeUnited Statesen_US
dc.identifier.scopusauthoridTian, XY=35768379500en_US
dc.identifier.scopusauthoridWong, WT=35932584500en_US
dc.identifier.scopusauthoridXu, A=7202655409en_US
dc.identifier.scopusauthoridLu, Y=55140513400en_US
dc.identifier.scopusauthoridZhang, Y=55140014200en_US
dc.identifier.scopusauthoridWang, L=55143471300en_US
dc.identifier.scopusauthoridCheang, WS=37025604300en_US
dc.identifier.scopusauthoridWang, Y=55140305000en_US
dc.identifier.scopusauthoridYao, X=7402529434en_US
dc.identifier.scopusauthoridHuang, Y=55141267100en_US

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