title: Hyperglycaemia protects the heart after myocardial infarction: aspects of programmed cell survival and cell death.
abstract: OBJECTIVE
  Exposure to a high glucose medium or diabetes has been found to protect the heart against ischaemia. The activation of antiapoptotic and proliferative factors seems to be involved in this cardioprotection. This study was designed to evaluate the role of hyperglycaemia in cardiac function, programmed cell survival, and cell death in diabetic rats after myocardial infarction (MI).
  
  
  RESULTS
  Male Wistar rats were divided into four groups (n = 8): control (C), diabetic (D), myocardial infarcted (MI), and diabetic myocardial infarcted (DI). The following measures were assessed in the left ventricle: size of MI, systolic and diastolic function by echocardiography, cytokines by ELISA (TNF-alpha, IL-1beta, IL-6, and IL-10), gene expression by real-time PCR (Bax, Fas, p53, Bcl-2, HIF1-alpha, VEGF, and IL8r), caspase-3 activity by spectrofluorometric assay, glucose transporter type 1 and 4 (GLUT-1 and GLUT-4) protein expression by western blotting, and capillary density and fibrosis by histological analysis. Systolic function was improved by hyperglycaemia in the DI group, and this was accompanied by no improvement in diastolic dysfunction, a reduction of 36% in MI size, reduced proinflammatory cytokines, apoptosis activation, and an increase in cell survival factors (HIF1-alpha, VEGFa and IL8r) assessed 15 days post-MI. Moreover, hyperglycaemia resulted in angiogenesis (increased capillary density) before and after MI, accompanied by a reduction in fibrosis.
  
  
  CONCLUSIONS
  Together, these results suggest that greater plasticity and cellular resistance to ischaemic injury result from chronic diabetic hyperglycaemia in rat hearts.
authors.affiliation: Hypertension Unit, Heart Institute InCor, University of São Paulo, Medical School, Av Eneas de Carvalho Aguiar 44, São Paulo, Brazil. chrismalfi@hotmail.com
authors.forename: Christiane
authors.initials: C
authors.lastname: Malfitano
authors.forename: Tatiana C
authors.initials: TC
authors.lastname: Alba Loureiro
authors.forename: Bruno
authors.initials: B
authors.lastname: Rodrigues
authors.forename: Raquel
authors.initials: R
authors.lastname: Sirvente
authors.forename: Vera Maria Cury
authors.initials: VM
authors.lastname: Salemi
authors.forename: Nara B
authors.initials: NB
authors.lastname: Rabechi
authors.forename: Silvia
authors.initials: S
authors.lastname: Lacchini
authors.forename: Rui
authors.initials: R
authors.lastname: Curi
authors.forename: Maria Claudia C
authors.initials: MC
authors.lastname: Irigoyen
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology; D053148:Caspase 3 / Q000378:metabolism; D002470:Cell Survival / Q000502:physiology; D016207:Cytokines / Q000032:analysis; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology*; D051246:Glucose Transport Proteins, Facilitative / Q000378:metabolism; D006321:Heart / Q000503:physiopathology*; D006943:Hyperglycemia / Q000503:physiopathology*; D008297:Male; D009203:Myocardial Infarction / Q000503:physiopathology*; D032383:Myocytes, Cardiac / Q000502:physiology*; D051381:Rats; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D016207:Cytokines; D051246:Glucose Transport Proteins, Facilitative; D014409:Tumor Necrosis Factor-alpha; D042461:Vascular Endothelial Growth Factor A; D053148:Caspase 3