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) beta 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) (1.5 mg/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 13 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 g 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 beta [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 13 ameliorated impaired angiogenesis by hyperglycemia in STZ-induced DM mice complicated by myocardial infarction. These results suggest a new possible indication of PKC 13 inhibitor for myocardial ischemia with DM. (Circ J 2012; 76: 943-949)