Adverse Effects of Simulated Hyper- and Hypo-Phosphatemia on Endothelial Cell Function and Viability 英文参考文献.docVIP

Adverse Effects of Simulated Hyper- and Hypo-Phosphatemia on Endothelial Cell Function and Viability 英文参考文献.doc

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Adverse Effects of Simulated Hyper- and Hypo-Phosphatemia on Endothelial Cell Function and Viability 英文参考文献

AdverseEffectsofSimulatedHyper-andHypo- PhosphatemiaonEndothelialCellFunctionandViability AiPeng1,2.,TianfuWu3.,CaihongZeng4,DineshRakheja2,JiankunZhu3,TingYe2,JackHutcheson3, NosratolaD.Vaziri5,ZhihongLiu4*,ChandraMohan3*,XinJ.Zhou2*¤ 1Department of Nephrology, Shanghai Tenth People’s Hospital of Tongji University, Shanghai, China, 2Department of Pathology, UT Southwestern Medical Center, Dallas,Texas,UnitedStatesofAmerica,3DivisionofRheumatology,DepartmentofInternalMedicine,UTSouthwesternMedicalCenter,Dallas,Texas,UnitedStatesof America, 4Research Institute of Nephrology, Jinling Hospital, Nanjing University School of Medicine, Nanjing, China, 5Division of Nephrology and Hypertension, UniversityofCaliforniaIrvine,Irvine,California,UnitedStatesofAmerica Abstract Background:Dysregulaitonofphosphatehomeostasisasoccursinchronickidneydiseaseisassociatedwithcardiovascular complications. It has been suggested that both hyperphosphatemia and hypophosphatemia can cause cardiovascular disease.Themolecularmechanismsbywhichhighorlowserumphosphatelevelsadverselyaffectcardiovascularfunction arepoorlyunderstood.Thepurposeofthisstudywastoexplorethemechanismsofendothelialdysfunctioninthepresence ofnon-physiologicphosphatelevels. Methodology/PrincipalFindings:Westudiedtheeffectsofsimulatedhyper-andhypophosphatemiainhumanumbilical vein endothelial cells in vitro. We found both simulated hyperphosphatemia and hypophosphatemia decrease eNOS expression and NO production. This was associated with reduced intracellular calcium, increased protein kinase C b2 (PKCb2),reducedcellviability,andincreasedapoptosis.Whilesimulatedhyperphosphatemiawasassociatedwithdecreased Akt/p-Akt,Bcl-xl/Baxratios,NFkB-p65andp-Erkabundance,simulatedhypophosphatemiawasassociatedwithincreased Akt/p-AktandBcl-xl/Baxratiosandp-Mek,p38,andp-p38abundance. Conclusions/Significance: This is the first demonstration of endothelial dysfunction with hypophosphatemia. Our data suggests that both hyperphosphatemia and hypo

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