Remote Preconditioning: Evaluating The Efficacy Of Cardioprotection In Type-2 Diabetes And Exploring The Mechanistic Role Of Exosomes
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چکیده
REMOTE PRECONDITIONING: EVALUATING THE EFFICACY OFCARDIOPROTECTION IN TYPE-2 DIABETES AND EXPLORING THEMECHANISTIC ROLE OF EXOSOMESbyJOSEPH WIDERMay 2017Advisor: Karin Przyklenk, Ph.D.Major: PhysiologyDegree: Doctor of PhilosophyRemote preconditioning is a promising and robust treatment for myocardialischemia/reperfusion injury that evokes cardioprotection through endogenous neuraland/or humoral signaling. A recent study has reported that protective signaling ismediated by exosomes through the circulation; however this concept is supported bylimited and inconsistent evidence. Despite overwhelming success in preclinical studies,the efficacy of remote preconditioning in human studies is inconclusive. Importantly, themajority of remote preconditioning studies use healthy animal models despite growingevidence that comorbidities, such as type-2 diabetes, may negatively influenceoutcomes. Nonetheless, the efficacy of remote preconditioning in the setting of type-2diabetes has not been investigated.Using an established model of myocardial ischemia/reperfusion in the Zuckermodel of type-2 diabetes and a model of hypoxia/reoxygenation in cultured HL-1cardiomyocytes we tested four hypotheses:i. remote preconditioning is ineffective in early-stage type-2 diabetes in vivo;ii. the traditional ultracentrifugation technique for exosomes isolating is inadequate
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