Dexamethasone treatment and ICAM-1 deficiency impair VEGF-induced angiogenesis in adult brain

TY - JOUR

T1 - Dexamethasone treatment and ICAM-1 deficiency impair VEGF-induced angiogenesis in adult brain

AU - Kasselman, Lora J.

AU - Kintner, Jennifer

AU - Sideris, Alexandra

AU - Pasnikowski, Elizabeth

AU - Krellman, Jason W.

AU - Shah, Sagar

AU - Rudge, John S.

AU - Yancopoulos, George D.

AU - Wiegand, Stanley J.

AU - Croll, Susan D.

PY - 2007/6

Y1 - 2007/6

N2 - Background: Infusion of exogenous vascular endothelial growth factor (VEGF) into adult brain at doses above 60 ng/day induces dramatic angiogenesis accompanied by vascular leak and inflammation. Blood vessels formed by this treatment are dilated and tortuous, exhibiting a pathological morphology. Pathological VEGF-induced angiogenesis is preceded by vascular leak and inflammation, which have been proposed to mediate subsequent angiogenesis. Methods: To test this hypothesis, we infused VEGF into the brains of adult rats to induce pathological angiogenesis. Some of these rats were treated with dexamethasone, a potent anti-inflammatory glucocorticoid, to inhibit inflammation and edema. Results: We demonstrate that inhibition of inflammation by treatment with dexamethasone significantly attenuated VEGF-induced pathological angiogenesis. To present converging evidence that inflammation may be important in this angiogenic process, we also demonstrate that mice genetically deficient in the inflammatory mediator intercellular adhesion molecule-1 have attenuated VEGF-induced angiogenesis. These same mice showed normal amounts of physiological angiogenesis in response to enriched environments, however, suggesting that a generalized reduction in vascular plasticity could not account for their poor angiogenic response to VEGF. Conclusions: Taken together, the data from these experiments suggest that the inflammation which occurs before or during VEGF-induced pathological brain angiogenesis plays a contributory role in the pathological angiogenic process.

AB - Background: Infusion of exogenous vascular endothelial growth factor (VEGF) into adult brain at doses above 60 ng/day induces dramatic angiogenesis accompanied by vascular leak and inflammation. Blood vessels formed by this treatment are dilated and tortuous, exhibiting a pathological morphology. Pathological VEGF-induced angiogenesis is preceded by vascular leak and inflammation, which have been proposed to mediate subsequent angiogenesis. Methods: To test this hypothesis, we infused VEGF into the brains of adult rats to induce pathological angiogenesis. Some of these rats were treated with dexamethasone, a potent anti-inflammatory glucocorticoid, to inhibit inflammation and edema. Results: We demonstrate that inhibition of inflammation by treatment with dexamethasone significantly attenuated VEGF-induced pathological angiogenesis. To present converging evidence that inflammation may be important in this angiogenic process, we also demonstrate that mice genetically deficient in the inflammatory mediator intercellular adhesion molecule-1 have attenuated VEGF-induced angiogenesis. These same mice showed normal amounts of physiological angiogenesis in response to enriched environments, however, suggesting that a generalized reduction in vascular plasticity could not account for their poor angiogenic response to VEGF. Conclusions: Taken together, the data from these experiments suggest that the inflammation which occurs before or during VEGF-induced pathological brain angiogenesis plays a contributory role in the pathological angiogenic process.

KW - Angiogenesis

KW - Brain

KW - Dexamethasone

KW - Enriched environments

KW - Inflammation

KW - Intercellular adhesion molecule-1

UR - https://www.scopus.com/pages/publications/34250754840

U2 - 10.1159/000101450

DO - 10.1159/000101450

M3 - Article

C2 - 17406120

SN - 1018-1172

VL - 44

SP - 283

EP - 291

JO - Journal of Vascular Research

JF - Journal of Vascular Research

IS - 4

ER -