PMID- 19736311 OWN - NLM STAT- MEDLINE DCOM- 20091207 LR - 20220711 IS - 1083-351X (Electronic) IS - 0021-9258 (Print) IS - 0021-9258 (Linking) VI - 284 IP - 45 DP - 2009 Nov 6 TI - Src-dependent STAT-3-mediated expression of monocyte chemoattractant protein-1 is required for 15(S)-hydroxyeicosatetraenoic acid-induced vascular smooth muscle cell migration. PG - 31142-55 LID - 10.1074/jbc.M109.012526 [doi] AB - To understand the role of human 15-lipoxygenase 1 (15-LOX1) in vascular wall remodeling, we have studied the effect of the major 15-LOX1 metabolite of arachidonic acid, 15(S)-hydroxyeicosatetraenoic acid (15(S)-HETE), on vascular smooth muscle cell (VSMC) migration both in vitro and in vivo. Among 5(S)-HETE, 12(S)-HETE, and 15(S)-HETE, 15(S)-HETE potentially stimulated more vascular smooth muscle cell (VSMC) migration. In addition, 15(S)-HETE-induced VSMC migration was dependent on Src-mediated activation of signal transducer and activator of transcription-3 (STAT-3). 15(S)-HETE also induced monocyte chemoattractant protein-1 (MCP-1) expression via Src-STAT-3 signaling, and neutralizing anti-MCP-1 antibodies completely negated 15(S)-HETE-induced VSMC migration. Cloning and characterization of a 2.6-kb MCP-1 promoter revealed the presence of four putative STAT-binding sites, and the site that is proximal to the transcription start site was found to be essential for 15(S)-HETE-induced Src-STAT-3-mediated MCP-1 expression. Rat carotid arteries that were subjected to balloon injury and transduced with Ad-15-LOX1 upon exposure to [(3)H]arachidonic acid ex vivo produced 15-HETE as a major eicosanoid and enhanced balloon injury-induced expression of MCP-1 in smooth muscle cells in Src and STAT-3-dependent manner in vivo. Adenovirus-mediated delivery of 15-LOX1 into rat carotid artery also led to recruitment and homing of macrophages to medial region in response to injury. In addition, transduction of Ad-15-LOX1 into arteries enhanced balloon injury-induced smooth muscle cell migration from media to intima and neointima formation. These results show for the first time that 15-LOX1-15(S)-HETE axis plays a major role in vascular wall remodeling after balloon angioplasty. FAU - Potula, Harihara S K AU - Potula HS AD - Department of Physiology, The University of Tennessee Health Science Center, Memphis, Tennessee 38163, USA. FAU - Wang, Dong AU - Wang D FAU - Quyen, Dong Van AU - Quyen DV FAU - Singh, Nikhlesh K AU - Singh NK FAU - Kundumani-Sridharan, Venkatesh AU - Kundumani-Sridharan V FAU - Karpurapu, Manjula AU - Karpurapu M FAU - Park, Edwards A AU - Park EA FAU - Glasgow, Wayne C AU - Glasgow WC FAU - Rao, Gadiparthi N AU - Rao GN LA - eng GR - R01 HL064165/HL/NHLBI NIH HHS/United States GR - HL064165/HL/NHLBI NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural DEP - 20090907 PL - United States TA - J Biol Chem JT - The Journal of biological chemistry JID - 2985121R RN - 0 (Chemokine CCL2) RN - 0 (Hydroxyeicosatetraenoic Acids) RN - 0 (STAT3 Transcription Factor) RN - EC 1.13.11.33 (Arachidonate 15-Lipoxygenase) RN - EC 2.7.10.2 (Proto-Oncogene Proteins pp60(c-src)) SB - IM MH - Animals MH - Arachidonate 15-Lipoxygenase/genetics/metabolism MH - Cell Line MH - *Cell Movement MH - Cells, Cultured MH - Chemokine CCL2/*genetics/metabolism MH - *Gene Expression Regulation MH - Humans MH - Hydroxyeicosatetraenoic Acids/*metabolism MH - In Vitro Techniques MH - Myocytes, Smooth Muscle/*cytology/metabolism MH - Proto-Oncogene Proteins pp60(c-src)/genetics/*metabolism MH - Rats MH - STAT3 Transcription Factor/genetics/*metabolism MH - Signal Transduction PMC - PMC2781513 EDAT- 2009/09/09 06:00 MHDA- 2009/12/16 06:00 PMCR- 2010/11/06 CRDT- 2009/09/09 06:00 PHST- 2009/09/09 06:00 [entrez] PHST- 2009/09/09 06:00 [pubmed] PHST- 2009/12/16 06:00 [medline] PHST- 2010/11/06 00:00 [pmc-release] AID - S0021-9258(20)38016-9 [pii] AID - M109.012526 [pii] AID - 10.1074/jbc.M109.012526 [doi] PST - ppublish SO - J Biol Chem. 2009 Nov 6;284(45):31142-55. doi: 10.1074/jbc.M109.012526. Epub 2009 Sep 7.