title: Cyclic strain stimulates monocyte chemotactic protein-1 mRNA expression in smooth muscle cells.
abstract: Hemodynamic forces are important determinants for the formation of atherosclerotic plaques. The recruitment of circulating monocytes into the arterial wall is an important step during atherogenesis. Monocyte chemotactic protein-1 (MCP-1) has been shown to be a key factor for monocyte transmigration. This study examined the effects of cyclic strain on MCP-1 mRNA expression levels of cultured rat aortic smooth muscle cells. The MCP-1 mRNA levels of aortic smooth muscle cells first increased as the duration of cyclic strain increased, reaching the maximum at 6-12 h, maintained at high levels throughout the 48-h strain period. To explore signaling pathways mediating cyclic strain-stimulated MCP-1 mRNA expression, we examined the involvement of tyrosine kinase and protein kinase C (PKC). Tyrosine kinase inhibitors, genistein and tyrphostin 51, at 50 microM blocked cyclic strain-stimulated MCP-1 mRNA expression. Preincubation with a PKC activator, phorbol 12-myristate 13-acetate (PMA), 2 microM, for 24 h to downregulate PKC did not decrease cyclic strain-induced MCP-1 mRNA expression. A 6-h incubation with 0. 1 microM PMA to activate PKC, which stimulated MCP-1 expression when applied alone, abolished the stimulatory effects of cyclic strain. A specific PKC inhibitor, calphostin C (0.1 microM), diminished cyclic strain-stimulated MCP-1 mRNA expression. Angiotensin II at 10 or 1,000 nM induced a moderate upregulation of MCP-1 mRNA, and no synergistic effects were observed between angiotensin II and cyclic strain. These results indicate that cyclic strain stimulates MCP-1 mRNA expression in smooth muscle cells through signaling pathway(s) mediated by tyrosine kinase activation.
authors.affiliation: Department of Anatomy, National Cheng Kung University, Tainan 701, Taiwan. mjiang@mail.ncku.edu.tw
authors.forename: M J
authors.initials: MJ
authors.lastname: Jiang
authors.forename: Y J
authors.initials: YJ
authors.lastname: Yu
authors.forename: Y L
authors.initials: YL
authors.lastname: Chen
authors.forename: Y M
authors.initials: YM
authors.lastname: Lee
authors.forename: L S
authors.initials: LS
authors.lastname: Hung
mesh_terms: D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D001161:Arteriosclerosis / Q000209:etiology; D002465:Cell Movement; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000235:genetics*; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D015870:Gene Expression / Q000187:drug effects; D009000:Monocytes / Q000502:physiology; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism*; D009281:Naphthalenes / Q000494:pharmacology; D019000:Phosphotyrosine / Q000378:metabolism; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D012333:RNA, Messenger / Q000235:genetics* / Q000378:metabolism*; D051381:Rats; D013314:Stress, Mechanical
chemical_list: D018932:Chemokine CCL2; D004791:Enzyme Inhibitors; D009281:Naphthalenes; D012333:RNA, Messenger; D000804:Angiotensin II; D019000:Phosphotyrosine; D011505:Protein-Tyrosine Kinases; D011493:Protein Kinase C; C058819:calphostin C