PKCδ impaired vessel formation and angiogenic factor expression in diabetic ischemic limb

  1. Pedro Geraldes1,*
  1. 1From the Clinical Research Center Étienne Le-Bel and Departments of Medicine, Division of Endocrinology, Université de Sherbrooke, Québec, Canada
  2. 2The Biotechnology Centre of Oslo, University of Oslo, Oslo, Norway
  1. *Corresponding author: Pedro Geraldes, Pedro.Geraldes{at}


Decreased collateral vessel formation in the diabetic peripheral limbs is characterised 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 VEGF and PDGF. The present study investigates the role of PKCδ in diabetes-induced poor collateral vessel formation and inhibition of angiogenic factors expression and actions. Ischemic adductors muscles of diabetic Prkcd+/+ mice exhibited reduced blood reperfusion, vascular density and number of small vessels as compared to non-diabetic Prkcd+/+ mice. By contrast, diabetic Prkcd-/- mice showed significant increased blood flow, capillary density and number of capillaries. Although expression of various PKC isoforms were unchanged, activation of PKCδ was increased in diabetic Prkcd+/+ mice. VEGF and PDGF mRNA and protein expression were decreased in muscles of diabetic Prkcd+/+ mice and normalized in diabetic Prkcd-/- mice. Furthermore, phosphorylation of VEGFR2 and PDGFR-β were blunted in diabetic Prkcd+/+ mice but elevated in diabetic Prkcd-/- mice. The inhibition of VEGFR2 and PDGFR-β activity was associated with increased SHP-1 expression. In conclusion, our data have uncovered the mechanisms by which PKCδ activation induced poor collateral vessel formation offering potential novel targets to regulate angiogenesis therapeutically in diabetic patients.

  • Received October 16, 2012.
  • Accepted March 29, 2013.

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