title: Phloretin attenuates hyperuricemia-induced endothelial dysfunction through co-inhibiting inflammation and GLUT9-mediated uric acid uptake.
abstract: Hyperuricemia is an important risk factor for cardiovascular and renal diseases. Phloretin had shown antioxidant and anti-inflammatory properties, but its role in endothelial injury is rarely reported. In this study, we aimed to investigate the protective effect of phloretin on UA-induced injury in human umbilical vein endothelial cells. The effects of UA and phloretin on cell viability, inflammation, THP-1 monocyte adhesion, endothelial cell tube formation, GLUT9 expression and UA uptake in human umbilical vein endothelial cells were evaluated. The changes of nuclear factor-kappa B/extracellular regulated protein kinases signalling were also analysed. Our results showed that UA reduced cell viability and tube formation, and increased inflammation and monocytes adhesion in human umbilical vein endothelial cells in a dose-dependent manner. In contrast, phloretin significantly attenuated pro-inflammatory factors expression and endothelial injury induced by UA. Phloretin inhibited the activation of extracellular regulated protein kinases/nuclear factor-kappa B pathway, and reduced GLUT9 and it mediated UA uptake in human umbilical vein endothelial cells. These results indicated that phloretin attenuated UA-induced endothelial injury via a synergic mechanism including direct anti-inflammatory effect and lowering cellular UA uptake. Our study suggested that phloretin might be a promising therapy for hyperuricemia-related cardiovascular diseases.
authors.affiliation: Key Laboratory of Transplant Engineering and Immunology, NHFPC; Regenerative Medicine Research Center, West China Hospital, Sichuan University, Chengdu, China.
authors.forename: Shuyun
authors.initials: S
authors.lastname: Liu
authors.affiliation: Key Laboratory of Transplant Engineering and Immunology, NHFPC; Regenerative Medicine Research Center, West China Hospital, Sichuan University, Chengdu, China.
authors.forename: Yujia
authors.initials: Y
authors.lastname: Yuan
authors.affiliation: Key Laboratory of Transplant Engineering and Immunology, NHFPC; Regenerative Medicine Research Center, West China Hospital, Sichuan University, Chengdu, China.
authors.forename: Yijie
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Key Laboratory of Transplant Engineering and Immunology, NHFPC; Regenerative Medicine Research Center, West China Hospital, Sichuan University, Chengdu, China.
authors.forename: Meng
authors.initials: M
authors.lastname: Zhao
authors.affiliation: Key Laboratory of Transplant Engineering and Immunology, NHFPC; Regenerative Medicine Research Center, West China Hospital, Sichuan University, Chengdu, China.
authors.forename: Younan
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Key Laboratory of Transplant Engineering and Immunology, NHFPC; Regenerative Medicine Research Center, West China Hospital, Sichuan University, Chengdu, China.
authors.forename: Jingqiu
authors.initials: J
authors.lastname: Cheng
authors.affiliation: Key Laboratory of Transplant Engineering and Immunology, NHFPC; Regenerative Medicine Research Center, West China Hospital, Sichuan University, Chengdu, China.
authors.forename: Yanrong
authors.initials: Y
authors.lastname: Lu
authors.affiliation: Key Laboratory of Transplant Engineering and Immunology, NHFPC; Regenerative Medicine Research Center, West China Hospital, Sichuan University, Chengdu, China.
authors.forename: Jingping
authors.identifier: 0000-0001-8364-639X
authors.initials: J
authors.lastname: Liu
mesh_terms: D002448:Cell Adhesion / Q000187:drug effects; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D051246:Glucose Transport Proteins, Facilitative / Q000235:genetics / Q000378:metabolism*; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D033461:Hyperuricemia / Q000503:physiopathology; D007249:Inflammation / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control*; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D010693:Phloretin / Q000494:pharmacology*; D034622:RNA Interference; D015398:Signal Transduction / Q000187:drug effects; D014527:Uric Acid / Q000493:pharmacokinetics / Q000494:pharmacology*
chemical_list: D051246:Glucose Transport Proteins, Facilitative; D016328:NF-kappa B; C411811:SLC2A9 protein, human; D014527:Uric Acid; D010693:Phloretin
keywords: GLUT9; Inflammation; endothelial dysfunction; phloretin; uric acid