Inhibition of protein kinase C β ameliorates impaired angiogenesis in type I diabetic mice complicating myocardial infarction.

BACKGROUND

In recent studies, the inhibition of protein kinase C (PKC) β has been shown to improve diabetic vascular complications. However, the effect on angiogenesis in myocardial ischemia with diabetes mellitus (DM) is still unknown.

METHODS AND RESULTS

Mice were divided into 3 groups: control, DM and DM+PKC-I groups (n=8, respectively). In the DM and DM+PKC-I groups, diabetes was induced by streptozotocin (STZ) (1.5mg/body i.p.) for 5 days. Next, left anterior descending artery (LAD) ligation was performed in all groups. In the DM+PKC-I group, PKC β inhibitor (Cat. No. 539654; 10 nmol/L) was administered from days 1 to 10. After 4 weeks of LAD ligation, the animals were killed. Microvascular density was significantly improved by PKC β inhibitor (control: 87.9±5.2/high-power field (HPF); DM: 51.4±6.9/HPF; PKC-I: 80.3±4.9/HPF; P<0.05). Expression of both vascular endothelial growth factor (VEGF) and endothelial nitric oxide synthase (eNOS), which was decreased in the DM group, were significantly improved by inhibition of PKC β [VEGF (DM: 0.36±0.11-fold and DM+PKC-I: 0.77±0.07-fold vs. control), eNOS (DM: 0.35±0.06-fold and DM+PKC-I: 0.73±0.08-fold vs. control); both P<0.05)].

CONCLUSIONS

Inhibition of PKC β ameliorated impaired angiogenesis by hyperglycemia in STZ-induced DM mice complicated by myocardial infarction. These results suggest a new possible indication of PKC β inhibitor for myocardial ischemia with DM.