The effect of diabetes on endothelin, interleukin-8 and vascular endothelial growth factor-mediated angiogenesis in rats.
In diabetes mellitus, there is a problem of both premature atherosclerosis as well as impaired collateralization. Studies were performed using the rat corneal angiogenesis model as a surrogate for collateralization to determine the effect of diabetes mellitus on endothelin (ET)-1, ET-3, vascular endothelial growth factor (VEGF) and interleukin-8 (IL-8)-mediated angiogenesis. In an initial group of experiments, streptozotocin-induced diabetes resulted in impairment of ET-1-mediated angiogenesis from 69% to 32%, but was only impaired from 74% to 59% for ET-3. When rats were fluid-resuscitated, mortality fell, and the incidence of inhibition of angiogenesis decreased for ET-1, but was still at 47%. Inhibition of ET-3-mediated angiogenesis in fluid-resuscitated rats was essentially unaffected from 74% to 75%. Studies of VEGF and IL-8 in fluid-resuscitated rats demonstrated that VEGF-mediated angiogenesis was only inhibited from 49% to 45%, but there was inhibition of IL-8-mediated angiogenesis from 62% to 31%. We concluded that there may be two mechanisms by which ET-1-mediated corneal angiogenesis is inhibited: a decrease in intravascular volume and dynamic forces affecting angiogenesis, and a direct effect of diabetes on some aspect of cell growth or angiogenic process. Diabetes also appeared to inhibit IL-8-mediated angiogenesis, but had very little or no effect on ET-3- or VEGF-mediated angiogenesis.
Department of Surgery, Nassau University Medical Center, 2201 Hempstead Turnpike, East Meadow, NY 11554, U.S.A. eugenebek@aol.com
Eugene L
EL
Bek
Marvin A
MA
McMillen
Paul
P
Scott
L D George
LD
Angus
Gerald W
GW
Shaftan
D000818:Animals; D016510:Corneal Neovascularization / Q000276:immunology / Q000378:metabolism*; D003921:Diabetes Mellitus, Experimental / Q000276:immunology / Q000378:metabolism / Q000503:physiopathology*; D016228:Endothelial Growth Factors / Q000378:metabolism*; D019332:Endothelin-1 / Q000494:pharmacology; D019334:Endothelin-3 / Q000494:pharmacology; D016232:Endothelins / Q000494:pharmacology*; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism*; D016209:Interleukin-8 / Q000378:metabolism*; D008222:Lymphokines / Q000378:metabolism*; D023421:Models, Animal; D051381:Rats; D017207:Rats, Sprague-Dawley; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D016228:Endothelial Growth Factors; D019332:Endothelin-1; D019334:Endothelin-3; D016232:Endothelins; D036341:Intercellular Signaling Peptides and Proteins; D016209:Interleukin-8; D008222:Lymphokines; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors