| Negative regulation of vascular smooth muscle cell migration by blood shear stress. | |
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MedLine Citation:
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PMID: 17012348 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Vortex blood flow with reduced blood shear stress in a vein graft has been hypothesized to promote smooth muscle cell (SMC) migration and intimal hyperplasia, pathological events leading to vein graft restenosis. To demonstrate that blood shear stress regulates these processes, we developed a modified vein graft model where the SMC response to reduced vortex blood flow was compared with that of control vein grafts. Vortex blood flow induced SMC migration and neointimal hyperplasia in control vein grafts, whereas reduction of vortex blood flow in the modified vein graft strongly suppressed these effects. A venous polymer implant with known fluid shear stress was employed to clarify the molecular mechanism of shear-dependent SMC migration in vivo. In the polymer implant, the phosphorylation of extracellular signal-regulated kinase (ERK1/2) and myosin light chain kinase (MLCK), found primarily in SMCs, increased from day 3 to day 5 and returned toward the control level from day 5 to day 10, with the peak phosphorylation associated with the maximal speed of SMC migration. Treatment with PD-98059 (an inhibitor specific to the ERK1/2 activator MEK1/2) significantly suppressed the phosphorylation of MLCK, suggesting a role for ERK1/2 in regulating the activity of MLCK. Treatment with PD-98059 or ML-7 (an inhibitor specific to MLCK) reduced shear stress-dependent SMC migration, resulting in an SMC distribution independent of fluid shear stress. These results suggest that fluid shear stress regulates SMC migration via the mediation of ERK1/2 and MLCK. |
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Authors:
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Jeremy Goldman; Lin Zhong; Shu Q Liu |
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Publication Detail:
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Type: Comparative Study; Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2006-09-29 |
Journal Detail:
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Title: American journal of physiology. Heart and circulatory physiology Volume: 292 ISSN: 0363-6135 ISO Abbreviation: Am. J. Physiol. Heart Circ. Physiol. Publication Date: 2007 Feb |
Date Detail:
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Created Date: 2007-02-08 Completed Date: 2007-03-20 Revised Date: 2009-11-19 |
Medline Journal Info:
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Nlm Unique ID: 100901228 Medline TA: Am J Physiol Heart Circ Physiol Country: United States |
Other Details:
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Languages: eng Pagination: H928-38 Citation Subset: IM |
Affiliation:
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Biomedical Engineering Department, Michigan Technological University, Houghton, MI 49931, USA. jgoldman@mtu.edu |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Anastomosis, Surgical Animals Aorta, Abdominal / surgery Blood Vessel Prosthesis Implantation Cell Movement* / drug effects Extracellular Signal-Regulated MAP Kinases / antagonists & inhibitors, metabolism Graft Occlusion, Vascular / pathology, physiopathology* Hyperplasia Jugular Veins / transplantation Male Models, Animal Muscle, Smooth, Vascular / pathology, physiopathology* Myocytes, Smooth Muscle / metabolism*, pathology Myosin-Light-Chain Kinase / antagonists & inhibitors, metabolism Phosphorylation Protein Kinase Inhibitors / pharmacology Pulsatile Flow Rats Rats, Sprague-Dawley Shear Strength* Signal Transduction* / drug effects Stress, Mechanical Time Factors |
| Chemical | |
Reg. No./Substance:
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0/Protein Kinase Inhibitors; EC 2.7.11.18/Myosin-Light-Chain Kinase; EC 2.7.11.24/Extracellular Signal-Regulated MAP Kinases |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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