title: Glycation abolishes the cardioprotective effects of albumin during ex vivo ischemia-reperfusion.
abstract: Hyperglycemia-induced oxidative stress plays a key role in the onset/progression 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, ± 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, oxidative 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 myocardial antioxidant capacity. However, such protective features are lost with glycation 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.
authors.affiliation: Cardio-Metabolic Research Group (CMRG), Department of Physiological Sciences, Stellenbosch University, Stellenbosch, South Africa.
authors.forename: Rudo F
authors.initials: RF
authors.lastname: Mapanga
authors.affiliation: Cardio-Metabolic Research Group (CMRG), Department of Physiological Sciences, Stellenbosch University, Stellenbosch, South Africa.
authors.forename: Danzil E
authors.initials: DE
authors.lastname: Joseph
authors.affiliation: Cardio-Metabolic Research Group (CMRG), Department of Physiological Sciences, Stellenbosch University, Stellenbosch, South Africa.
authors.forename: Marco
authors.identifier: http://orcid.org/0000-0002-4218-515X
authors.initials: M
authors.lastname: Saieva
authors.affiliation: Inserm UMR 1188 Diabète athérothrombose Thérapies Réunion Océan Indien (DéTROI) Université de La Réunion Plateforme CYROI, Saint Denis de La Réunion, France.
authors.forename: Florence
authors.initials: F
authors.lastname: Boyer
authors.affiliation: Inserm UMR 1188 Diabète athérothrombose Thérapies Réunion Océan Indien (DéTROI) Université de La Réunion Plateforme CYROI, Saint Denis de La Réunion, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Rondeau
authors.affiliation: Inserm UMR 1188 Diabète athérothrombose Thérapies Réunion Océan Indien (DéTROI) Université de La Réunion Plateforme CYROI, Saint Denis de La Réunion, France.
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Bourdon
authors.affiliation: Cardio-Metabolic Research Group (CMRG), Department of Physiological Sciences, Stellenbosch University, Stellenbosch, South Africa mfessop@sun.ac.za.
authors.forename: M Faadiel
authors.initials: MF
authors.lastname: Essop
mesh_terms: D000418:Albumins / Q000008:administration & dosage* / Q000378:metabolism*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002316:Cardiotonic Agents / Q000008:administration & dosage* / Q000378:metabolism; D017127:Glycation End Products, Advanced / Q000378:metabolism*; D006031:Glycosylation; D006321:Heart / Q000187:drug effects* / Q000503:physiopathology; D006943:Hyperglycemia / Q000150:complications / Q000378:metabolism* / Q000517:prevention & control; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D015428:Myocardial Reperfusion Injury / Q000150:complications / Q000378:metabolism* / Q000517:prevention & control; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D012710:Serum Albumin, Bovine / Q000008:administration & dosage / Q000378:metabolism; D000075462:Serum Albumin, Human / Q000008:administration & dosage / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism; D000072105:Superoxide Dismutase-1 / Q000378:metabolism; D000099156:Superoxide Dismutase 2
chemical_list: D000418:Albumins; D002316:Cardiotonic Agents; D017127:Glycation End Products, Advanced; D012710:Serum Albumin, Bovine; D000075462:Serum Albumin, Human; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1; D000099156:Superoxide Dismutase 2; C000606292:Sod1 protein, rat
keywords: Albumin; cardiac dysfunction; glycation; hyperglycemia; ischemia‐reperfusion; oxidative stress