This Article Full Text Full Text (PDF) Data Supplement All Versions of this Article: 23/8/1377    most recent 01.ATV.0000081740.65173.D1v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Kim, W. Articles by Park, S. K. Search for Related Content PubMed PubMed Citation Articles by Kim, W. Articles by Park, S. K. Pubmed/NCBI databases Substance via MeSH Related Collections Health policy and outcome research Acute coronary syndromes

(Arteriosclerosis, Thrombosis, and Vascular Biology. 2003;23:1377.)
© 2003 American Heart Association, Inc.

Vascular Biology

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

Won Kim; Sang-Ok Moon; Sik Lee; Mi Jeong Sung; Sung Hoon Kim; Sung Kwang Park

From the Department of Internal Medicine, Research Institute of Clinical Medicine, Chonbuk National University Medical School, Chonju, Republic of Korea.

Correspondence to Sung Kwang Park, MD, PhD, Department of Internal Medicine, Chonbuk National University Medical School, 634-18, Keum-Am dong, Chonju, 560-180, Republic of Korea. 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

This article has been cited by other articles:

				D. Ribatti, M. T. Conconi, and G. G. Nussdorfer Nonclassic Endogenous Novel Regulators of Angiogenesis Pharmacol. Rev., June 1, 2007; 59(2): 185 - 205. [Abstract] [Full Text] [PDF]

				K. Podar, G. Tonon, M. Sattler, Y.-T. Tai, S. LeGouill, H. Yasui, K. Ishitsuka, S. Kumar, R. Kumar, L. N. Pandite, et al. The small-molecule VEGF receptor inhibitor pazopanib (GW786034B) targets both tumor and endothelial cells in multiple myeloma PNAS, December 19, 2006; 103(51): 19478 - 19483. [Abstract] [Full Text] [PDF]

				S.-O. Moon, W. Kim, M. J. Sung, S. Lee, K. P. Kang, D. H. Kim, S. Y. Lee, J.-N. So, and S. K. Park Resveratrol Suppresses Tumor Necrosis Factor-{alpha}-Induced Fractalkine Expression in Endothelial Cells Mol. Pharmacol., July 1, 2006; 70(1): 112 - 119. [Abstract] [Full Text] [PDF]

				K. Miyashita, H. Itoh, H. Arai, T. Suganami, N. Sawada, Y. Fukunaga, M. Sone, K. Yamahara, T. Yurugi-Kobayashi, K. Park, et al. The Neuroprotective and Vasculo-Neuro-Regenerative Roles of Adrenomedullin in Ischemic Brain and Its Therapeutic Potential Endocrinology, April 1, 2006; 147(4): 1642 - 1653. [Abstract] [Full Text] [PDF]

				M. J. Sung, W. Kim, S. Y. Ahn, C.-H. Cho, G. Y. Koh, S.-O. Moon, D. H. Kim, S. Lee, K. P. Kang, K. Y. Jang, et al. Protective Effect of {alpha}-Lipoic Acid in Lipopolysaccharide-Induced Endothelial Fractalkine Expression Circ. Res., October 28, 2005; 97(9): 880 - 890. [Abstract] [Full Text] [PDF]

				N. Sengupta, S. Caballero, R. N. Mames, J. M. Butler, E. W. Scott, and M. B. Grant The Role of Adult Bone Marrow-Derived Stem Cells in Choroidal Neovascularization Invest. Ophthalmol. Vis. Sci., November 1, 2003; 44(11): 4908 - 4913. [Abstract] [Full Text] [PDF]