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Inhibition of Vascular Endothelial Growth Factor-induced Endothelial Cell Differentiation by Intravenous Immunoglobulin and Methylprednisolone

Korean Journal of Pediatrics 2005;48(8):886-893.
Published online August 15, 2005.
Inhibition of Vascular Endothelial Growth Factor-induced Endothelial Cell Differentiation by Intravenous Immunoglobulin and Methylprednisolone
Hyoun Ah Choi, Kyung Hwa Ha, Jong Seo Yoon, Yoon Lee, Joon Sung Lee, Ji Whan Han
Department of Pediatrics, College of Medicine, The Catholic University of Korea, Seoul, Korea
혈관내막 성장인자에 의해 유도된 내막세포 분화에 대한 정맥용 면역글로불린과 메틸프레드니솔론의 효과
최현아, 하경화, 윤종서, 이윤, 이준성, 한지환
가톨릭대학교 의과대학 소아과학교실
Correspondence: 
Ji Whan Han, Email: han59@catholic.ac.kr
Abstract
Purpose
: Kawasaki disease is the most common cause of systemic vasculitis in children less than 5 years of age. Recent immunohistochemistry findings suggest that many vascular growth factors play a role in the formation of the coronary artery lesions. Active remodeling of the coronary artery lesions in Kawasaki disease continues in the form of intimal proliferation and neoangiogenesis for several years after the onset of the disease. Intravenous immunoglobulin(IVIG) and corticosteroid have been used in the treatment of Kawasaki disease but the exact mechanism is not clear. We have investigated that IVIG and corticosteroid inhibited vascular endothelial growth factor(VEGF)- induced tube formation of endothelial cells in vitro on Matrigel assay.
Methods
: Human umbilical vein endothelial cells(HUVECs) were cultured and seeded on Matrigel coated 24 well plates in medium with or without the following agents : VEGF, VEGF plus IVIG, VEGF plus VEGF antibody, VEGF plus methylprednisolone, VEGF, IVIG plus methylprednisolone for 18 hours. The total length of tube structures in each photograph was quantified.
Results
: IVIG significantly inhibited the proliferation of HUVECs. The inhibitory effect of IVIG was also reversible. In the meantime, VEGF induced the differentiation of HUVECs into capillary like structures on Matrigel, which was inhibited by VEGF antibody in a dose-dependent manner. Interestingly, IVIG and methylprednisolone inhibited VEGF-induced tube formation of HUVECs. IVIG was more effective in inhibition than methylprednisolone alone.
Conclusion
: We revealed that VEGF induced the differentiation of HUVECs and this effect was inhibited by IVIG and methylprednisolone.
Key Words: Endothelial cell , Vascular endothelial growth factor(VEGF) , Intravenous immunoglobulin(IVIG) , Methylprednisolone


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