Myocardial infarction in diabetic rats: role of hyperglycaemia on infarct size and early expression of hypoxia-inducible factor 1.
Diabetologia
; 45(8): 1172-81, 2002 Aug.
Article
em En
| MEDLINE
| ID: mdl-12189448
ABSTRACT
AIMS/HYPOTHESIS:
This study aimed to evaluate the effects of hyperglycaemia on the evolution of myocardial infarction and the expression of the transcriptional factor for angiogenesis hypoxia-inducible factor 1alpha (HIF-1alpha) in the rat.METHODS:
We studied the effects of streptozotocin induced diabetes on infarct size and HIF-1 alpha gene expression. These parameters were also evaluated in isolated hearts of non-diabetic rat, in condition of high glucose concentration.RESULTS:
In streptozotocin (STZ)-diabetic rats (in vivo study), myocardial infarct size was greater (p<0.01) in hyperglycaemic rats (22 mmol/l) than in normoglycaemic (7 mmol/l) or non-diabetic rats. In euglycaemic conditions, basal expression of HIF-1alpha mRNA was not appreciable, but increased steadily after ischaemia (762+/-86%, p<0.001); this response was blunted in hyperglycaemic STZ-rats (6.8+/-6% of the control, p<0.001) and improved in euglycaemic STZ-rats (58+/-10%). The changes in myocardial Rac1 mRNA expression paralleled those of HIF-1alpha. In isolated hearts from non-diabetic rats (in vitro study), perfusion with high glucose (33 mmol/l) produced an infarct size (58+/-2% of the area at risk) not different from that obtained in hyperglycaemic STZ-rats (57+/-2%). Similar changes in the expression of HIF-1alpha and Rac1, which were prevented by glutathione infusion (0.3 mmol/l) were also observed. CONCLUSION/INTERPRETATION:
Both hyperglycaemia and high glucose concentrations increased basal HIF-1alpha and Rac1 expression, suggesting a state of pseudohypoxia. These findings show that myocardial infarct size in the rat is increased in hyperglycaemic conditions and is associated with a reduced expression of the HIF-1alpha gene. These changes are reversed, totally or partially, by normoglycaemia or glutathione suggesting a role for reactive oxygen species generation brought about by hyperglycaemia.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Fatores de Transcrição
/
Diabetes Mellitus Experimental
/
Angiopatias Diabéticas
/
Hiperglicemia
/
Infarto do Miocárdio
Limite:
Animals
Idioma:
En
Revista:
Diabetologia
Ano de publicação:
2002
Tipo de documento:
Article