Key result
Type 2 diabetes is associated with reduced myocardial expression of HIF-1alpha and VEGF and increased levels of iNOS, nitrotyrosine, and superoxide anion during ischemia (P<0.001).
Why the study?
Does type 2 diabetes alter the expression of myocardial angiogenesis factors and oxidative stress markers during acute coronary syndromes?
Observational (n=49)
Does type 2 diabetes alter the expression of myocardial angiogenesis factors and oxidative stress markers during acute coronary syndromes?
p-value: p=<0.001
Type 2 diabetes impairs the myocardial angiogenic response to ischemia by reducing HIF-1alpha and VEGF expression while simultaneously increasing oxidative stress.
Reduced HIF-1α/VEGF response in diabetic myocardium during ischemia may explain poor collaterals; leaves open whether pathway targeting improves outcomes in unstable angina.
Inadequate angiogenic response to ischemia in diabetic myocardium could result in poor collateral formation. Because hypoxia-inducible factor (HIF)-1alpha is a transcriptional activator of vascular endothelial growth factor (VEGF) and is critical for initiating angiogenic responses to hypoxia, we investigated the expression of HIF-1alpha and VEGF in specimens of human heart tissue to elucidate the molecular responses to myocardial ischemia in diabetic patients during unstable angina. Moreover, accumulation of a marker of protein nitration nitrotyrosine, as well as the superoxide anion (O(2)(-)) levels and inducible nitric oxide synthase (iNOS), were evaluated. Ventricular biopsy specimens from 15 type 2 diabetic and 14 nondiabetic patients presenting with unstable angina (ischemic group) and from 20 patients (11 type 2 diabetic and 9 nondiabetic patients) who underwent coronary bypass surgery without angina within the preceding 10 days (control group) were collected during coronary bypass surgery. Nondiabetic patients had higher HIF-1alpha and VEGF expressions compared with diabetic patients (P < 0.001). As compared with nondiabetic specimens, diabetic specimens showed higher levels of both iNOS mRNA and protein levels (P < 0.001) associated with the highest tissue levels of nitrotyrosine and O(2)(-) (P < 0.001). Diabetes is associated with increased myocardial tissue levels of iNOS, O(2)(-), and nitrotyrosine and reduced expression of myocardial angiogenesis factors during ischemia.
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Marfella et al. (2004) conducted an observational in Acute Coronary Syndromes / Type 2 Diabetes (n=49). Type 2 diabetes vs. Nondiabetic status was evaluated on Myocardial expression of HIF-1alpha, VEGF, iNOS, nitrotyrosine, and O(2)(-) (p=<0.001). Type 2 diabetes is associated with reduced myocardial expression of HIF-1alpha and VEGF and increased levels of iNOS, nitrotyrosine, and superoxide anion during ischemia (P<0.001).