Selective Endothelial Overexpression of Arginase II Induces Endothelial Dysfunction and Hypertension and Enhances Atherosclerosis in Mice 英文参考文献.docVIP

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Selective Endothelial Overexpression of Arginase II Induces Endothelial Dysfunction and Hypertension and Enhances Atherosclerosis in Mice 英文参考文献.doc

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Selective Endothelial Overexpression of Arginase II Induces Endothelial Dysfunction and Hypertension and Enhances Atherosclerosis in Mice 英文参考文献

SelectiveEndothelialOverexpressionofArginaseII InducesEndothelialDysfunctionandHypertensionand EnhancesAtherosclerosisinMice BorisL.Vaisman1.,KarenL.Andrews2*.,SachaM.L.Khong2.,KatherineC.Wood1,XiaoL.Moore2, YiFu2,DianeM.Kepka-Lenhart3,SidneyM.MorrisJr.3,AlanT.Remaley1,JayeP.F.Chin-Dusting2 1Cardiovascular-Pulmonary Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland, United States of America, 2Vascular Pharmacology Laboratory,Baker IDIHeartandDiabetes Institute, Melbourne,Victoria, Australia, 3Departments ofMicrobiology andMolecular Genetics, University of Pittsburgh,SchoolofMedicine,Pittsburgh,Pennsylvania,UnitedStatesofAmerica Abstract Background: Cardiovascular disorders associated with endothelial dysfunction, such as atherosclerosis, have decreased nitricoxide(NO)bioavailability.ArginaseinthevasculaturecancompetewitheNOSforL-arginineandhasbeenimplicated inatherosclerosis.Theaimofthisstudywastoevaluatetheeffectofendothelial-specificelevationofarginaseIIexpression onendothelialfunctionandthedevelopmentofatherosclerosis. Methodology/Principal Findings: Transgenic mice on aC57BL/6 background withendothelial-specific overexpression of humanarginaseII(hArgII)geneunderthecontroloftheTie2promoterwereproduced.ThehArgIImicehadelevatedtissue arginaseactivityexceptinliverandinresidentperitonealmacrophages,confirmingendothelialspecificityofthetransgene. Using small-vessel myography, aorta from these mice exhibited endothelial dysfunction when compared to their non- transgenic littermatecontrols. Thebloodpressure ofthehArgII mice was17% higher thantheirlittermate controlsand, whencrossedwithapoE2/2mice,hArgIImicehadincreasedaorticatheroscleroticlesions. Conclusion:WeconcludethatoverexpressionofarginaseIIintheendotheliumisdetrimentaltothecardiovascularsystem. Citation: Vaisman BL, Andrews KL, Khong SML, Wood KC, Moore XL, et al. (2012) Selective Endothelial Overexpression of Arginase II Induces Endothelial DysfunctionandH