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