Doxycycline Does Not Influence Established Abdominal Aortic Aneurysms in Angiotensin II-Infused Mice 英文参考文献.docVIP

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Doxycycline Does Not Influence Established Abdominal Aortic Aneurysms in Angiotensin II-Infused Mice 英文参考文献.doc

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Doxycycline Does Not Influence Established Abdominal Aortic Aneurysms in Angiotensin II-Infused Mice 英文参考文献

DoxycyclineDoesNotInfluenceEstablishedAbdominal AorticAneurysmsinAngiotensinII-InfusedMice XiaojieXie1,2,HongLu1,JessicaJ.Moorleghen1,DeborahA.Howatt1,DebraL.Rateri1,LisaA.Cassis3, AlanDaugherty1,3 * 1Saha Cardiovascular Research Center, University of Kentucky, Lexington, Kentucky, United States of America, 2Key Laboratory for Diagnosis and Treatment of CardiovascularDiseaseofZhejiangProvince,DepartmentofCardiology,SecondAffiliatedHospital,ZhejiangUniversityCollegeofMedicine,Hangzhou,Zhejiang,People’s RepublicofChina,3GraduateCenterforNutritionalSciences,UniversityofKentucky,Lexington,Kentucky,UnitedStatesofAmerica Abstract Background:Thereisnoprovenmedicalapproachtoattenuatingexpansionandruptureofabdominalaorticaneurysms (AAAs). One approach that is currently being investigated is the use of doxycycline. Despite being primarily used as an antimicrobial drug, doxycycline has been proposed to function in reducing AAA expansion. Doxycycline is effective in reducingtheformationinthemostcommonlyusedmousemodelsofAAAswhenadministeredpriortotheinitiationofthe disease.ThepurposeofthecurrentstudywastodeterminetheeffectsofdoxycyclineonestablishedAAAswhenitwas administeredatadosethatproducestherapeuticserumconcentrations. Methods and Results: LDL receptor 2/2 male mice fed a saturated-fat supplemented diet were infused with AngII (1,000ng/kg/min)viamini-osmoticpumpsfor28days.UponverificationofAAAformationbynoninvasivehighfrequency ultrasonography, mice were stratified based on aortic lumen diameters, and continuously infused with AngII while also administeredeithervehicleordoxycycline(100mg/kg/day)indrinkingwaterfor56days.Administrationofdoxycyclineled to serum drug concentrations of 2.360.6mg/ml. Doxycycline administration had no effect on serum cholesterol concentrations and systolic blood pressures. Doxycycline administration did not prevent progressive aortic dilation as determinedbytemporalmeasurementsoflumendimensionsusinghighfrequencyultrasound.ThislackofeffectonAAA