PMID- 15498848 OWN - NLM STAT- MEDLINE DCOM- 20050303 LR - 20210206 IS - 0006-4971 (Print) IS - 0006-4971 (Linking) VI - 105 IP - 4 DP - 2005 Feb 15 TI - Monocyte chemoattractant protein-1-induced angiogenesis is mediated by vascular endothelial growth factor-A. PG - 1405-7 AB - 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-A(165) (VEGF-A(165)) 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-A(165) and completely inhibited by a VEGF inhibitor, Flt(2-11). The inhibition of RhoA small G protein did not affect MCP-1-induced VEGF-A(165) 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. FAU - Hong, Kyung Hee AU - Hong KH AD - Department of Cardiology, University of Ulsan College of Medicine, Asan Medical Center, 388-1 Pungnap-2 dong Songpa-gu 138-736, Seoul, South Korea. FAU - Ryu, Jewon AU - Ryu J FAU - Han, Ki Hoon AU - Han KH LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20041021 PL - United States TA - Blood JT - Blood JID - 7603509 RN - 0 (Angiogenesis Inducing Agents) RN - 0 (CCL2 protein, human) RN - 0 (Chemokine CCL2) RN - 0 (HIF1A protein, human) RN - 0 (Hypoxia-Inducible Factor 1, alpha Subunit) RN - 0 (RNA, Messenger) RN - 0 (Transcription Factors) RN - 0 (Vascular Endothelial Growth Factor A) SB - IM MH - Angiogenesis Inducing Agents/*administration & dosage MH - Animals MH - Aorta, Abdominal/physiology MH - Aorta, Thoracic/physiology MH - Cells, Cultured MH - Chemokine CCL2/*administration & dosage/metabolism MH - Endothelium, Vascular/cytology/metabolism/physiology MH - Humans MH - Hypoxia-Inducible Factor 1, alpha Subunit MH - Male MH - Neovascularization, Physiologic/*physiology MH - RNA, Messenger/biosynthesis MH - Rats MH - Rats, Sprague-Dawley MH - Transcription Factors/biosynthesis/genetics MH - Vascular Endothelial Growth Factor A/biosynthesis/genetics/*physiology EDAT- 2004/10/23 09:00 MHDA- 2005/03/04 09:00 CRDT- 2004/10/23 09:00 PHST- 2004/10/23 09:00 [pubmed] PHST- 2005/03/04 09:00 [medline] PHST- 2004/10/23 09:00 [entrez] AID - S0006-4971(20)45859-8 [pii] AID - 10.1182/blood-2004-08-3178 [doi] PST - ppublish SO - Blood. 2005 Feb 15;105(4):1405-7. doi: 10.1182/blood-2004-08-3178. Epub 2004 Oct 21.