{"doi":"10.1161/circresaha.111.262170","title":"Uncoupling Protein-2 Protects Endothelial Function in Diet-Induced Obese Mice","abstract":"<jats:sec>\n            <jats:title>\n              <jats:underline>Rationale:</jats:underline>\n            </jats:title>\n            <jats:p>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.</jats:p>\n          </jats:sec>\n          <jats:sec>\n            <jats:title>\n              <jats:underline>Objective:</jats:underline>\n            </jats:title>\n            <jats:p>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.</jats:p>\n          </jats:sec>\n          <jats:sec>\n            <jats:title>\n              <jats:underline>Methods and Results:</jats:underline>\n            </jats:title>\n            <jats:p>\n              Endothelium-dependent relaxation (EDR) in aortae and mesenteric arteries in response to acetylcholine was measured in wire myograph. Flow-mediated vasodilatation in 2\n              <jats:sup>nd</jats:sup>\n              -order mesenteric arteries was measured in pressure myograph. ROS production is measured by CM-H\n              <jats:sub>2</jats:sub>\n              DCFDA and DHE fluorescence. High-glucose exposure reduced EDR in mouse aortae, which was exaggerated in\n              <jats:italic>UCP2</jats:italic>\n              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\n              <jats:italic>UCP2KO</jats:italic>\n              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\n              <jats:italic>en face</jats:italic>\n              endothelium of aorta and mesenteric artery of DIO mice, whereas UCP2 deficiency enhanced ROS production.\n            </jats:p>\n          </jats:sec>\n          <jats:sec>\n            <jats:title>\n              <jats:underline>Conclusions:</jats:underline>\n            </jats:title>\n            <jats:p>UCP2 preserves endothelial function through increasing nitric oxide bioavailability secondary to the inhibition of ROS production in the endothelium of obese diabetic mice.</jats:p>\n          </jats:sec>","journal":"Circulation Research","year":2012,"id":680733,"datarank":0.7423139835567254,"base_score":4.948759890378168,"endowment":4.948759890378168,"self_citation_contribution":0.7423139835567254,"citation_network_contribution":0.0,"self_endowment_contribution":0.7423139835567254,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":140,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1778550,"name":"Wing Tak Wong","orcid":null,"position":1,"is_corresponding":false},{"id":385995,"name":"Aimin Xu","orcid":"0000-0002-0668-033X","position":2,"is_corresponding":false},{"id":1047333,"name":"Ye Lu","orcid":"0000-0003-3698-5596","position":3,"is_corresponding":false},{"id":887376,"name":"Yang Zhang","orcid":"0000-0003-3383-7889","position":4,"is_corresponding":false},{"id":346834,"name":"Li Wang","orcid":"0000-0003-4959-0729","position":5,"is_corresponding":false},{"id":1043104,"name":"Wai San Cheang","orcid":"0000-0002-1152-7997","position":6,"is_corresponding":false},{"id":1204114,"name":"Yu Wang","orcid":"0000-0002-8683-6196","position":7,"is_corresponding":false},{"id":488123,"name":"Xiaoqiang Yao","orcid":"0000-0002-0687-8186","position":8,"is_corresponding":false},{"id":1409994,"name":"Yu Huang","orcid":"0000-0003-3699-4708","position":9,"is_corresponding":false},{"id":435405,"name":"Xiao Yu Tian","orcid":"0000-0003-3472-9898","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Uncoupling Protein-2 Protects Endothelial Function in Diet-Induced Obese Mice","abstract":"<jats:sec>\n            <jats:title>\n              <jats:underline>Rationale:</jats:underline>\n            </jats:title>\n            <jats:p>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.</jats:p>\n          </jats:sec>\n          <jats:sec>\n            <jats:title>\n              <jats:underline>Objective:</jats:underline>\n            </jats:title>\n            <jats:p>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.</jats:p>\n          </jats:sec>\n          <jats:sec>\n            <jats:title>\n              <jats:underline>Methods and Results:</jats:underline>\n            </jats:title>\n            <jats:p>\n              Endothelium-dependent relaxation (EDR) in aortae and mesenteric arteries in response to acetylcholine was measured in wire myograph. Flow-mediated vasodilatation in 2\n              <jats:sup>nd</jats:sup>\n              -order mesenteric arteries was measured in pressure myograph. ROS production is measured by CM-H\n              <jats:sub>2</jats:sub>\n              DCFDA and DHE fluorescence. High-glucose exposure reduced EDR in mouse aortae, which was exaggerated in\n              <jats:italic>UCP2</jats:italic>\n              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\n              <jats:italic>UCP2KO</jats:italic>\n              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\n              <jats:italic>en face</jats:italic>\n              endothelium of aorta and mesenteric artery of DIO mice, whereas UCP2 deficiency enhanced ROS production.\n            </jats:p>\n          </jats:sec>\n          <jats:sec>\n            <jats:title>\n              <jats:underline>Conclusions:</jats:underline>\n            </jats:title>\n            <jats:p>UCP2 preserves endothelial function through increasing nitric oxide bioavailability secondary to the inhibition of ROS production in the endothelium of obese diabetic mice.</jats:p>\n          </jats:sec>","is_dataset_classified":null,"base_score":4.948759890378168,"endowment":4.948759890378168,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"22461387","pmcid":null,"openalex_id":"https://openalex.org/W2149630312","authors":[],"funders":[],"total_grants":0,"fwci":9.271,"citation_percentile":0.9864969,"influential_citations":0,"citation_trend":[{"year":2012,"count":1},{"year":2013,"count":17},{"year":2014,"count":20},{"year":2015,"count":17},{"year":2016,"count":14},{"year":2017,"count":11},{"year":2018,"count":13},{"year":2019,"count":7},{"year":2020,"count":4},{"year":2021,"count":10},{"year":2022,"count":8},{"year":2023,"count":1},{"year":2024,"count":9},{"year":2025,"count":6},{"year":2026,"count":2}],"oa_status":"bronze","license":null,"oa_locations":[{"url":"https://www.ahajournals.org/doi/pdf/10.1161/CIRCRESAHA.111.262170","host_type":"journal"},{"url":"https://www.ahajournals.org/doi/pdf/10.1161/CIRCRESAHA.111.262170","host_type":"publisher"},{"url":"https://www.ahajournals.org/doi/full/10.1161/CIRCRESAHA.111.262170","host_type":"publisher"},{"url":"https://doi.org/10.1161/circresaha.111.262170","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/22461387","host_type":"repository"},{"url":"http://hdl.handle.net/10722/163487","host_type":"repository"}],"fields_of_study":["Adipose Tissue and Metabolism","Cardiovascular Disease and Adiposity","Adipokines, Inflammation, and Metabolic Diseases"],"mesh_terms":["Uncoupling Protein 2","Animals","Aorta, Thoracic","Disease Models, Animal","Dose-Response Relationship, Drug","Endothelium, Vascular","Enzyme Inhibitors","Glucose","Humans","Ion Channels","Male","Mesenteric Arteries","Mice, Inbred C57BL","Myography","Nitric Oxide","Obesity","Organ Culture Techniques","Regional Blood Flow","Time Factors","Transfection","Vasodilation","Vasodilator Agents","Free Radical Scavengers","Reactive Oxygen Species","Mice, Knockout","Oxidative Stress","Nitric Oxide Synthase","Mitochondrial Proteins","Mice","Diet, High-Fat","Human Umbilical Vein Endothelial Cells"],"keywords":["Myograph","Mesenteric arteries","Endocrinology","Internal medicine","Vasodilation","Endothelial dysfunction","Nitric oxide","Endothelium","Electrical impedance myography","Reactive oxygen species","Medicine","Nitric oxide synthase","Chemistry","Artery","Biochemistry"],"sdg_mappings":[],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-17T15:58:57.232529Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}