Adrenomedullin Reduces VEGF-Induced Endothelial Adhesion Molecules and Adhesiveness Through a Phosphatidylinositol 3′-Kinase Pathway

• Published in: Arteriosclerosis, thrombosis, and vascular biology Vol. 23; no. 8; pp. 1377 - 1383
• Main Authors: Kim, Won, Moon, Sang-Ok, Lee, Sik, Sung, Mi Jeong, Kim, Sung Hoon, Park, Sung Kwang
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA American Heart Association, Inc 01.08.2003; Hagerstown, MD Lippincott
• Subjects: Adrenomedullin; Atherosclerosis (general aspects, experimental research); Biological and medical sciences; Blood and lymphatic vessels; Cardiology. Vascular system; Cell Adhesion - physiology; Cell Adhesion Molecules - genetics; Cell Adhesion Molecules - metabolism; Cells, Cultured; E-Selectin - genetics; E-Selectin - metabolism; Endothelium, Vascular - metabolism; Enzyme Activation; Gene Expression - physiology; Humans; Intercellular Adhesion Molecule-1 - genetics; Intercellular Adhesion Molecule-1 - metabolism; Leukocytes - physiology; Medical sciences; Peptides - genetics; Peptides - metabolism; Phosphatidylinositol 3-Kinases - metabolism; Phosphorylation; Protein-Serine-Threonine Kinases; Proto-Oncogene Proteins - metabolism; Proto-Oncogene Proteins c-akt; RNA, Messenger - analysis; Signal Transduction; Vascular Cell Adhesion Molecule-1 - genetics; Vascular Cell Adhesion Molecule-1 - metabolism; Vascular Endothelial Growth Factor A - metabolism; Vasculitis - physiopathology; Human; Cell culture; Vascular cell adhesion molecule 1; endothelial cells; Intercellular adhesion molecule 1; Enzyme; Pathogenesis; Transferases; Adrenomedullin; Cardiovascular disease; Adhesion; Vascular disease; Phosphatidylinositol; Vascular endothelium growth factor; Kinase; adhesion molecules; inflammation; vascular endothelial growth factor; Atherosclerosis
• DOI: 10.1161/01.ATV.0000081740.65173.D1
• ISSN: 1079-5642

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.