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Glycation abolishes the cardioprotective effects of albumin during ex vivo ischemia-reperfusion

Abstract : Hyperglycemia-induced oxidative stress plays a key role in the onset/progres-sion of cardiovascular diseases. For example, it can trigger formation of advanced glycation end (AGE) products with ischemia-reperfusion performed under hyperglycemic conditions. For this study, we hypothesized that albumin modified by glycation loses its unique cardioprotective properties in the setting of ischemia-reperfusion under high glucose conditions. Here, ex vivo rat heart perfusions were performed under simulated normo-and hyperglycemic conditions, that is Krebs-Henseleit buffer containing 11 mmol/L and 33 mmol/L glucose, respectively, AE normal or glycated albumin preparations. The perfusion protocol consisted of a 60 min stabilization step that was followed by 20 min of global ischemia and 60 min reperfusion. Additional experiments were completed to determine infarct sizes in response to 20 min regional ischemia and 120 min reperfusion. At the end of perfusions, heart tissues were isolated and evaluated for activation of the AGE pathway, oxida-tive stress, and apoptosis. Our data reveal that native bovine serum albumin treatment elicited cardioprotection (improved functional recovery, decreased infarct sizes) under high glucose conditions together with enhanced myocar-dial antioxidant capacity. However, such protective features are lost with gly-cation where hearts displayed increased infarct sizes and poor functional recovery versus native albumin treatments. Myocardial antioxidant capacity was also lowered together with activation of the intracellular AGE pathway. These data therefore show that although albumin acts as a cardioprotective agent during ischemia-reperfusion, it loses its cardioprotective and antioxidant properties when modified by glycation.
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Submitted on : Wednesday, August 28, 2019 - 7:48:19 AM
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Rudo F. Mapanga, Danzil Joseph, Marco Saieva, Florence Boyer, Philippe Rondeau, et al.. Glycation abolishes the cardioprotective effects of albumin during ex vivo ischemia-reperfusion. Physiological Reports, Wiley, 2017, 5 (2), pp.e13107. ⟨10.14814/phy2.13107⟩. ⟨hal-02272666⟩



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