Vascular Dysfunction Induced by AGE is Mediated by VEGF via Mechanisms Involving Reactive Oxygen Species, Guanylate Cyclase, and Protein Kinase C

Abstract

These observations indicate potentially important roles for oxygen free-radicals and nitric oxide in mediating permeability and blood flow changes induced by glycated proteins via mechanisms involving increased protein kinase C activity and VEGF production. Striking similarities in the mechanism by which hyperglycemia and glycated proteins induce vascular dysfunction suggest that a common pathway mediates effects of these different metabolic imbalances on vascular dysfunction.

Signalling pathways involved in retinal endothelial cell proliferation induced by advanced glycation end products: inhibitory effect of gliclazide

“…To the best of our knowledge, this is the first report showing that AGEs induce PKC-b activation in retinal endothelial cells. These findings together with previous results, which show that PKC-b activation is associated with increased endothelial permeability [21] and retinal dysfunction in diabetic animals [22,23], support a key role for the activation of this PKC isoform in abnormal retinal haemodynamics associated with diabetes. It has been proposed that some of the PKC activation in the diabetic retina could be the result of excessive oxidative stress.…”

Periodontal healing after application of enamel matrix derivative in surgical supra/infrabony periodontal defects in rats with streptozotocin‐induced diabetes

“…Chronic hyperglycemia associated with diabetes not only decreases bone metabolism but also increases secretion of proinflammatory cytokines such as interleukin 1 (14,15), tumor necrosis factor-a (15)(16)(17) and prostaglandin E 2 (18). Furthermore, it is also reported that hyperglycemia can induce periodontal tissue destruction associated with the formation of advanced glycation end products (15,19,20), vascular dysfunction (21), altered immune function (22) and decreased collagen synthesis (23)(24)(25).…”

Methylglyoxal‐induced Fibronectin gene expression through Ras‐mediated NADPH oxidase activation in renal mesangial cells

“…9 It has been demonstrated that upregulated oxidative stress promotes vascular dysfunction, lipid peroxidation and glycooxidative molecule production in diabetes. [10][11][12] Enhanced superoxide production has been found in renal cortex from streptozotocin-induced diabetic rats. 13 Thus, it is a reasonable implication and believed that O2 -, as a primary signalling molecule, promotes the production of reactive oxygen species (ROS) downstream, which act as signalling molecules further to cause diabetic nephropathy through a redox-sensitive pathway.…”