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.


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.
Department of Cardiovascular Surgery, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tsukuba, Japan.
Akihiko
A
Ikeda
Shonosuke
S
Matsushita
Yuzuru
Y
Sakakibara
D000818:Animals; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D015153:Blotting, Western; D003921:Diabetes Mellitus, Experimental / Q000150:complications / Q000188:drug therapy* / Q000201:enzymology / Q000503:physiopathology; D003922:Diabetes Mellitus, Type 1 / Q000150:complications / Q000188:drug therapy* / Q000201:enzymology / Q000503:physiopathology; D003925:Diabetic Angiopathies / Q000188:drug therapy* / Q000201:enzymology / Q000209:etiology / Q000503:physiopathology; D051379:Mice; D008810:Mice, Inbred C57BL; D055806:Microvessels / Q000187:drug effects* / Q000201:enzymology / Q000503:physiopathology; D009203:Myocardial Infarction / Q000150:complications / Q000188:drug therapy* / Q000201:enzymology / Q000503:physiopathology; D009206:Myocardium / Q000473:pathology; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D011493:Protein Kinase C / Q000037:antagonists & inhibitors* / Q000378:metabolism; D064546:Protein Kinase C beta; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*; D013997:Time Factors; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
D001786:Blood Glucose; D047428:Protein Kinase Inhibitors; D042461:Vascular Endothelial Growth Factor A; C467480:vascular endothelial growth factor A, mouse; D052250:Nitric Oxide Synthase Type III; C496315:Nos3 protein, mouse; D011493:Protein Kinase C; D064546:Protein Kinase C beta