Oleanolic Acid A Novel Cardioprotective Agent That Blunts Hyperglycemia-Induced Contractile Dysfunction 英文参考文献.docVIP

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Oleanolic Acid A Novel Cardioprotective Agent That Blunts Hyperglycemia-Induced Contractile Dysfunction 英文参考文献.doc

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Oleanolic Acid A Novel Cardioprotective Agent That Blunts Hyperglycemia-Induced Contractile Dysfunction 英文参考文献

OleanolicAcid:ANovelCardioprotectiveAgentThat BluntsHyperglycemia-InducedContractileDysfunction RudoF.Mapanga1,UthraRajamani1,NonkululekoDlamini2,MakhosazaneZungu-Edmondson2, RoisinKelly-Laubscher3,MohammedShafiullah4,AthiqWahab4,MohamedY.Hasan4, MohamedA.Fahim4,PhilippeRondeau5,EmmanuelBourdon5,M.FaadielEssop1* 1Cardio-MetabolicResearchGroup(CMRG),DepartmentofPhysiologicalSciences,StellenboschUniversity,Stellenbosch,SouthAfrica,2DisciplineofPhysiology,School ofMedicalSciences,UniversityofKwaZulu-Natal,Durban,SouthAfrica,3DepartmentofHumanBiology,FacultyofHealthSciences,UniversityofCapeTown,Observatory, SouthAfrica,4FacultyofMedicineandHealthSciences,UnitedArabEmiratesUniversity,Al-Ain,UnitedArabEmirates,5Grouped’Etudesurl’InflammationChroniqueet l’Obe′site′ (GEICO),Universite′ deLaRe′union,SaintDenisdeLaRe′union,France Abstract Diabetesconstitutesamajorhealthchallenge.Sincecardiovascularcomplicationsarecommonindiabeticpatientsthiswill further increase the overall burden of disease. Furthermore, stress-induced hyperglycemia in non-diabetic patients with acute myocardial infarction is associated with higher in-hospital mortality. Previous studies implicate oxidative stress, excessivefluxthroughthehexosaminebiosyntheticpathway(HBP)andadysfunctionalubiquitin-proteasomesystem(UPS) as potential mediators of this process. Since oleanolic acid (OA; a clove extract) possesses antioxidant properties, we hypothesizedthatitattenuatesacuteandchronichyperglycemia-mediatedpathophysiologicmolecularevents(oxidative stress,apoptosis,HBP,UPS)andtherebyimprovescontractilefunctioninresponsetoischemia-reperfusion.Weemployed several experimental systems: 1) H9c2 cardiac myoblasts were exposed to 33mM glucose for 48hr vs. controls (5mM glucose);andsubsequentlytreatedwithtwoOAdoses(20and50mM)for6and24hr,respectively;2)Isolatedrathearts were perfused ex vivo with Krebs-Henseleit buffer containing 33mM glucose vs. controls (11mM glucose) for 60min, followedby20minglobalischemiaand60minreperf