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Blood, 15 February 2005, Vol. 105, No. 4, pp. 1405-1407.
Prepublished online as a Blood First Edition Paper on October 21, 2004; DOI 10.1182/blood-2004-08-3178.


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CHEMOKINES
Brief report

Monocyte chemoattractant protein-1–induced angiogenesis is mediated by vascular endothelial growth factor-A

Kyung Hee Hong, Jewon Ryu, and Ki Hoon Han

From the Division of Cardiology, Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.

Monocyte chemoattractant protein-1 (MCP-1) has been recognized as an angiogenic chemokine. In the present study, we investigated the detailed mechanism by which MCP-1 induces angiogenesis. We found that MCP-1 up-regulated hypoxia-inducible factor 1{alpha} (HIF-1{alpha}) gene expression in human aortic endothelial cells (HAECs), which induced vascular endothelial growth factor-A165 (VEGF-A165) expression in the aortic wall and HAECs through activation of p42/44 mitogen-activated protein kinase (MAPK). In vivo angiogenesis assay using chick chorioallantoic membrane (CAM) showed that MCP-1–induced angiogenesis was as potent as that induced by VEGF-A165 and completely inhibited by a VEGF inhibitor, Flt2-11. The inhibition of RhoA small G protein did not affect MCP-1–induced VEGF-A165 production and secretion but completely blocked both MCP-1– and VEGF-A–induced new vessel formation, as determined by CAM assay. These results suggest that MCP-1–induced angiogenesis is composed largely of 2 sequential steps: the induction of VEGF-A gene expression by MCP-1 and the subsequent VEGF-A–induced angiogenesis.


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