Vascular dysfunction induced by elevated glucose levels in rats is mediated by vascular endothelial growth factor.

Abstract

The purpose of these experiments was to investigate a potential role for vascular endothelial growth factor (VEGF) in mediating vascular dysfunction induced by increased glucose flux via the sorbitol pathway. Skin chambers were mounted on the backs of Sprague-Dawley rats and 1 wk later, granulation tissue in the chamber was exposed twice daily for 7 d to 5 mM glucose, 30 mM glucose, or 1 mM sorbitol in the presence and absence of neutralizing VEGF antibodies. Albumin permeation and blood flow were increased two-to three-fold by 30 mM glucose and 1 mM sorbitol; these increases were prevented by coadministration of neutralizing VEGF antibodies. Blood flow and albumin permeation were increased ‫ف‬ 2.5-fold 1 h after topical application of recombinant human VEGF and these effects were prevented by nitric oxide synthase (NOS) inhibitors (aminoguanidine and N G -monomethyl L -arginine). Topical application of a superoxide generating system increased albumin permeation and blood flow and these changes were markedly attenuated by VEGF antibody and NOS inhibitors. Application of sodium nitroprusside for 7 d or the single application of a calcium ionophore, A23187, mimicked effects of glucose, sorbitol, and VEGF on vascular dysfunction and the ionophore effect was prevented by coadministration of aminoguanidine. These observations suggest a potentially important role for VEGF in mediating vascular dysfunction induced by "hypoxia-like" cytosolic metabolic imbalances (reductive stress, increased superoxide, and nitric oxide production) linked to increased flux of glucose via the sorbitol pathway. ( J. Clin. Invest. 1997. 99:2192-2202.)

Effects of Oxygen Administration on the Circulating Vascular Endothelial Growth Factor (VEGF) Levels in Patients with Obstructive Sleep Apnea Syndrome

“…VEGFhas been shown to be an important factor in the pathogenesis of vascularrelated diseases, including the growth of tumors, vascular dysfunction in diabetes mellitus, and atherosclerosis of the coronary arteries (13,27,28). The increased VEGFproduction found in OSASpatients might contribute to new vessel formation in ischemic and atherosclerotic vascular regions.…”

Vascular Endothelial Growth Factor (VEGF)-Induced Retinal Vascular Permeability Is Mediated by Intercellular Adhesion Molecule-1 (ICAM-1)

“…11 Briefly, purified monomer bovine serum albumin (BSA; 1 mg, Sigma, St. Louis, MO) was iodinated with 1 mCi of 131 I or 125 I using the iodogen method. Polyethylene tubing (0.58 mm internal diameter) was used to cannulate the right jugular vein and the left or right iliac artery.…”

“…Tissue and arterial samples were weighed and counted in a ␥-spectrometer (Beckman 5500, Irvine, CA). The data were corrected for background and a quantitative index of [ 125 I] tissue clearance was calculated as previously described 11 …”

Putative pathophysiological role of growth factors and cytokines in experimental diabetic kidney disease

“…The finding that EGF has short-term effects on renal function [163,164] opens some possibilities for a physiological role of EGF in the kidney. Although one study [148] reported reduced urinary EGF excretion after reduction of renal mass, others reported increased urinary EGF excretion [165], increased renal EGF synthesis and a transiently increased amount of immunoreactive EGF in distal kidney tubules after unilateral nephrectomy [166]. In experimental diabetes a possible role for EGF in the early renal enlargement has been proposed.…”