on June 12, 2003
Published online before print June 12, 2003, doi: 10.1161/01.ATV.0000081740.65173.D1
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Submitted on October 16, 2002
Accepted on May 7, 2003
Adrenomedullin Reduces VEGF-Induced Endothelial Adhesion Molecules and Adhesiveness Through a Phosphatidylinositol 3'-Kinase Pathway
Won Kim ;
From the Department of Internal Medicine, Research Institute of Clinical Medicine, Chonbuk National University Medical School, Chonju, Republic of Korea.
* To whom correspondence should be addressed. E-mail: parksk{at}moak.chonbuk.ac.kr.
Objective--In the initial phase of inflammation, vascular endothelial growth factor (VEGF) can act as a proinflammatory cytokine by inducing adhesion molecules that bind leukocytes to endothelial cells. Adrenomedullin (AM) is known to act as either a proinflammatory or an anti-inflammatory agent. In this study, we examined the effects of AM on adhesion molecule expression and leukocyte adhesiveness in VEGF-stimulated human umbilical vein endothelial cells.
Methods and Results--When stimulated with VEGF, the mRNAs of intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and E-selectin were dose-dependently upregulated. AM inhibited the VEGF-induced protein and mRNA expression of ICAM-1, VCAM-1, and E-selectin. Phosphatidylinositol 3'-kinase inhibitor and a dominant-negative form of Akt significantly inhibited the suppressive effect of AM on VEGF-induced adhesion molecule expression. Thus, AM inhibits VEGF-stimulated ICAM-1 and VCAM-1 expression through a phosphatidylinositol 3'-kinase/Akt pathway. AM reduced VEGF-induced endothelial adhesiveness for leukocytes.
Conclusions--These results suggest that AM might have an anti-inflammatory role in controlling VEGF-induced adhesion molecule gene expression and adhesiveness toward leukocytes in endothelial cells.
Key words: adrenomedullin • vascular endothelial growth factor • adhesion molecules • endothelial cells • inflammation
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