| First Author | Lizotte F | Year | 2013 |
| Journal | Diabetes | Volume | 62 |
| Issue | 8 | Pages | 2948-57 |
| PubMed ID | 23557702 | Mgi Jnum | J:208971 |
| Mgi Id | MGI:5565446 | Doi | 10.2337/db12-1432 |
| Citation | Lizotte F, et al. (2013) PKCdelta impaired vessel formation and angiogenic factor expression in diabetic ischemic limbs. Diabetes 62(8):2948-57 |
| abstractText | Decreased collateral vessel formation in diabetic peripheral limbs is characterized by abnormalities of the angiogenic response to ischemia. Hyperglycemia is known to activate protein kinase C (PKC), affecting the expression and activity of growth factors such as vascular endothelial growth factor (VEGF) and platelet-derived growth factor (PDGF). The current study investigates the role of PKCdelta in diabetes-induced poor collateral vessel formation and inhibition of angiogenic factors expression and actions. Ischemic adductor muscles of diabetic Prkcd(+/+) mice exhibited reduced blood reperfusion, vascular density, and number of small vessels compared with nondiabetic Prkcd(+/+) mice. By contrast, diabetic Prkcd(-/-) mice showed significant increased blood flow, capillary density, and number of capillaries. Although expression of various PKC isoforms was unchanged, activation of PKCdelta was increased in diabetic Prkcd(+/+) mice. VEGF and PDGF mRNA and protein expression were decreased in the muscles of diabetic Prkcd(+/+) mice and were normalized in diabetic Prkcd(-/-) mice. Furthermore, phosphorylation of VEGF receptor 2 (VEGFR2) and PDGF receptor-beta (PDGFR-beta) were blunted in diabetic Prkcd(+/+) mice but elevated in diabetic Prkcd(-/-) mice. The inhibition of VEGFR2 and PDGFR-beta activity was associated with increased SHP-1 expression. In conclusion, our data have uncovered the mechanisms by which PKCdelta activation induced poor collateral vessel formation, offering potential novel targets to regulate angiogenesis therapeutically in diabetic patients. |
