+ Site Statistics
References:
54,258,434
Abstracts:
29,560,870
PMIDs:
28,072,757
+ Search Articles
+ PDF Full Text Service
How our service works
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ Translate
+ Recently Requested

Negative regulation of vascular smooth muscle cell migration by blood shear stress



Negative regulation of vascular smooth muscle cell migration by blood shear stress



American Journal of Physiology. Heart and Circulatory Physiology 292(2): H928-H938



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.

Please choose payment method:






(PDF emailed within 0-6 h: $19.90)

Accession: 049664206

Download citation: RISBibTeXText

PMID: 17012348

DOI: 10.1152/ajpheart.00821.2006


Related references

Negative regulation of vascular smooth muscle cell migration by blood shear stress. American Journal of Physiology Heart and Circulatory Physiology 292(2): H928-H938, 2007

Role of blood shear stress in the regulation of vascular smooth muscle cell migration. IEEE Transactions on Bio-Medical Engineering 48(4): 474-483, 2001

Shear stress protects against endothelial regulation of vascular smooth muscle cell migration in a coculture system. Endothelium 13(3): 171-180, 2006

Regulation of vascular smooth muscle cell turnover by endothelial cell-secreted microRNA-126: role of shear stress. Circulation Research 113(1): 40-51, 2013

Rho-GDP dissociation inhibitor alpha downregulated by low shear stress promotes vascular smooth muscle cell migration and apoptosis: a proteomic analysis. Cardiovascular Research 80(1): 114-122, 2008

Effect of fluid shear stress on migration of vascular smooth muscle cells in cocultured model. Annals of Biomedical Engineering 34(3): 408-415, 2006

Increasing our IQ of vascular smooth muscle cell migration with IQGAP1. Focus on "IQGAP1 links PDGF receptor-β signal to focal adhesions involved in vascular smooth muscle cell migration: role in neointimal formation after vascular injury". American Journal of Physiology. Cell Physiology 305(6): C579-C580, 2014

Regulation of shear-dependent smooth muscle cell migration by MAPKs. FASEB Journal 15(4): A87, March 7, 2001

Shear stress activates Akt during vascular smooth muscle cell reorientation. Biotechnology and Applied Biochemistry 55(2): 85-90, 2010

Vascular smooth muscle cell glycocalyx modulates shear-induced proliferation, migration, and NO production responses. American Journal of Physiology. Heart and Circulatory Physiology 300(1): H76-H83, 2011

The tetraspanin CD9 is a negative modulator of human vascular smooth muscle cell migration. Journal of Submicroscopic Cytology & Pathology 32(3): 484, July, 2000

Less REST, more vascular disease? Regulation of cell cycle and migration of vascular smooth muscle cells. Cell Cycle 5(2): 129-131, 2005

Laminar shear stress stimulates vascular smooth muscle cell apoptosis via the Akt pathway. Journal of Cellular Physiology 216(2): 389-395, 2008

Cell segmentation of vascular smooth muscle cells under shear stress using image processing. Sichuan Daxue Xuebao (Ziran Kexueban) 44(2): 284-288, 2007

Subnormal shear stress-induced intimal thickening requires medial smooth muscle cell proliferation and migration. Experimental and Molecular Pathology 72(2): 150-160, 2002