Effects on protein kinase C-β inhibition on glomerular vascular endothelial growth factor expression and endothelial cells in advanced experimental diabetic nephropathy

Ruboxistaurin is an inhibitor of the β isoform of protein kinase C (PKC-β) that reduces the actions of vascular endothelial growth factor (VEGF) and attenuates the progression of diabetic retinopathy. In the glomerulus VEGF is constitutively expressed where it likely has a role in maintaining endothelial cell integrity, particularly in disease states. Given its potential use in diabetic nephropathy, we sought to determine the effects of PKC-β inhibition on VEGF and glomerular endothelial cells in experimental diabetic nephropathy. Studies were conducted in (mRen-2)27 rat, a transgenic rodent with hypertension and an enhanced renin-angiotensin system that following induction of diabetes with streptozotocin develops many of the features of diabetic nephropathy. Moreover, to mimic the clinical context, the effects of PKC-β inhibition were examined both with and without concomitant angiotensin-converting enzyme (ACE) inhibitor therapy. Diabetic Ren-2 rats were randomized to receive either vehicle, the ACE inh...