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Myocardial infarction in diabetic rats: role of hyperglycaemia on infarct size and early expression of hypoxia-inducible factor 1
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Myocardial infarction in diabetic rats: role of hyperglycaemia on infarct size and early expression of hypoxia-inducible factor 1
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Journal Article
Myocardial infarction in diabetic rats: role of hyperglycaemia on infarct size and early expression of hypoxia-inducible factor 1
2002
Overview
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.
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.
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.
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.
Publisher
Springer,Springer Nature B.V
Subject
/ Animals
/ Associated diseases and complications
/ Biological and medical sciences
/ Diabetes
/ Diabetes Mellitus, Experimental - blood
/ Diabetes Mellitus, Experimental - complications
/ Diabetes Mellitus, Experimental - physiopathology
/ Diabetes. Impaired glucose tolerance
/ Diabetic Angiopathies - metabolism
/ Diabetic Angiopathies - pathology
/ DNA-Binding Proteins - metabolism
/ Endocrine pancreas. Apud cells (diseases)
/ Glucose
/ Hypoxia
/ Hypoxia-Inducible Factor 1, alpha Subunit
/ Ischemia
/ Male
/ Myocardial Infarction - etiology
/ Myocardial Infarction - metabolism
/ Myocardial Infarction - pathology
/ Nuclear Proteins - metabolism
/ rac1 GTP-Binding Protein - metabolism
/ Rats
