title: Type 2 diabetic obese db/db mice are refractory to myocardial ischaemic post-conditioning in vivo: potential role for Hsp20, F1-ATPase δ and Echs1.
abstract: Ischaemic post-conditioning (PostC) is a clinically relevant cardioprotective modality that has been confirmed in many species including human. It remains unknown if PostC can still protect heart in Type 2 diabetes, a rapidly growing disease in the world. This study investigated the efficacy of PostC in the leptin receptor-deficient db/db mice, which possess Type 2 diabetic characteristics including obesity, hyperglycaemia and hyperleptinaemia. Adult male C57BL/6J wild-type (WT) and db/db mice were anaesthetized, mechanically ventilated and subjected to left coronary artery occlusion for 30 min. followed by 24 hrs of reperfusion. For the PostC groups, the hearts underwent six cycles of 10 sec. of reperfusion and 10 sec. of re-occlusion at the onset of reperfusion. The mice were sacrificed at the end of 24 hrs reperfusion for infarct size measurement. PostC significantly reduced infarct size in WT mice (n = 6/group; P < 0.05), but not in the db/db mice. To identify alterations in protein expression by PostC, proteomic analyses were performed in the heart samples using two-dimensional differential in-gel electrophoresis with three CyDye labelling, followed by mass spectrometry. The results show that mitochondrial proteins (F(1)-ATPase γ and Echs1) were down-regulated by PostC in WT heart. Such change was absent in the db/db heart. On the other hand, PostC reduced Hsp20 in the diabetic heart. In summary, PostC fails to protect Type 2 diabetic mice against ischaemia-reperfusion injury. The potential protein targets for the loss of PostC may include F(1)-ATPase γ, Echs1 and Hsp20 that could regulate cellular ATP consumption/production and defense response to ischaemic stress.
authors: Division of Cardiology, Department of Internal Medicine, VCU Pauley Heart Center, Virginia Commonwealth University, Richmond, VA 23298-0204, USA.
authors: Shu-Guang
authors: SG
authors: Zhu
authors: Lei
authors: L
authors: Xi
authors: Rakesh C
authors: RC
authors: Kukreja
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D001835:Body Weight; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000503:physiopathology*; D004746:Enoyl-CoA Hydratase / Q000502:physiology*; D050886:HSP20 Heat-Shock Proteins / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D024101:Mitochondrial Proteins / Q000502:physiology*; D015428:Myocardial Reperfusion Injury / Q000503:physiopathology*; D006180:Proton-Translocating ATPases / Q000502:physiology*; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
chemical_list: D001786:Blood Glucose; D050886:HSP20 Heat-Shock Proteins; D024101:Mitochondrial Proteins; D006180:Proton-Translocating ATPases; D004746:Enoyl-CoA Hydratase