Abstract
Objective: Vascular smooth muscle cell (SMC) migration is critical to the development of atherosclerosis and neointimal hyperplasia. Hemodynamic forces such as shear stress and cyclic strain stimulate endothelial cell signal-transduction pathways, resulting in the secretion of several factors, including SMC chemoattractants such as platelet-derived growth factor (PDGF). We hypothesized that mechanical forces stimulate endothelial cells to secrete SMC chemoattractants to induce migration via the mitogen-activated protein kinase (MAPK) pathway. Methods: Bovine aortic endothelial cells were exposed to shear stress, cyclic strain, or static conditions for 16 hours. The resulting conditioned medium was used as a SMC chemoattractant in a Boyden chamber. Activation of SMC extracellular signal-regulated protein kinase 1/2 (ERK1/2) was assessed by Western blot analysis. Pathways were inhibited with anti-PDGF-BB or anti-interleukin-1α (IL-1α) antibodies, or the ERK1/2 upstream pathway inhibitor PD98059. Results: Conditioned medium from endothelial cells exposed to shear stress corresponding to arterial levels of shear stress stimulated SMC migration but lower levels of shear stress or cyclic strain did not. Both PDGF-BB and IL-1α were secreted into the conditioned medium by endothelial cells stimulated with shear stress. Both PDGF-BB and IL-1α stimulated SMC chemotaxis but were not synergistic, and both stimulated SMC ERK1/2 phosphorylation. Inhibition of PDGF-BB or IL-1α inhibited SMC chemotaxis and ERK1/2 phosphorylation. Conclusion: Shear stress stimulates endothelial cells to secrete several SMC chemoattractants, including PDGF-BB and IL-1α; both PDGF-BB and IL-1α stimulate SMC chemotaxis via the ERK1/2 signal-transduction pathway. These results suggest that the response to vascular injury may have a common pathway amenable to pharmacologic manipulation.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 321-331 |
| Number of pages | 11 |
| Journal | Journal of Vascular Surgery |
| Volume | 41 |
| Issue number | 2 |
| DOIs | |
| State | Published - Jan 1 2005 |
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All Science Journal Classification (ASJC) codes
- Surgery
- Cardiology and Cardiovascular Medicine
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Shear stress-stimulated endothelial cells induce smooth muscle cell chemotaxis via platelet-derived growth factor-BB and interleukin-1α. / Dardik, Alan; Yamashita, Akimasa; Aziz, Faisal; Asada, Hidenori; Sumpio, Bauer E.
In: Journal of Vascular Surgery, Vol. 41, No. 2, 01.01.2005, p. 321-331.Research output: Contribution to journal › Article
TY - JOUR
T1 - Shear stress-stimulated endothelial cells induce smooth muscle cell chemotaxis via platelet-derived growth factor-BB and interleukin-1α
AU - Dardik, Alan
AU - Yamashita, Akimasa
AU - Aziz, Faisal
AU - Asada, Hidenori
AU - Sumpio, Bauer E.
PY - 2005/1/1
Y1 - 2005/1/1
N2 - Objective: Vascular smooth muscle cell (SMC) migration is critical to the development of atherosclerosis and neointimal hyperplasia. Hemodynamic forces such as shear stress and cyclic strain stimulate endothelial cell signal-transduction pathways, resulting in the secretion of several factors, including SMC chemoattractants such as platelet-derived growth factor (PDGF). We hypothesized that mechanical forces stimulate endothelial cells to secrete SMC chemoattractants to induce migration via the mitogen-activated protein kinase (MAPK) pathway. Methods: Bovine aortic endothelial cells were exposed to shear stress, cyclic strain, or static conditions for 16 hours. The resulting conditioned medium was used as a SMC chemoattractant in a Boyden chamber. Activation of SMC extracellular signal-regulated protein kinase 1/2 (ERK1/2) was assessed by Western blot analysis. Pathways were inhibited with anti-PDGF-BB or anti-interleukin-1α (IL-1α) antibodies, or the ERK1/2 upstream pathway inhibitor PD98059. Results: Conditioned medium from endothelial cells exposed to shear stress corresponding to arterial levels of shear stress stimulated SMC migration but lower levels of shear stress or cyclic strain did not. Both PDGF-BB and IL-1α were secreted into the conditioned medium by endothelial cells stimulated with shear stress. Both PDGF-BB and IL-1α stimulated SMC chemotaxis but were not synergistic, and both stimulated SMC ERK1/2 phosphorylation. Inhibition of PDGF-BB or IL-1α inhibited SMC chemotaxis and ERK1/2 phosphorylation. Conclusion: Shear stress stimulates endothelial cells to secrete several SMC chemoattractants, including PDGF-BB and IL-1α; both PDGF-BB and IL-1α stimulate SMC chemotaxis via the ERK1/2 signal-transduction pathway. These results suggest that the response to vascular injury may have a common pathway amenable to pharmacologic manipulation.
AB - Objective: Vascular smooth muscle cell (SMC) migration is critical to the development of atherosclerosis and neointimal hyperplasia. Hemodynamic forces such as shear stress and cyclic strain stimulate endothelial cell signal-transduction pathways, resulting in the secretion of several factors, including SMC chemoattractants such as platelet-derived growth factor (PDGF). We hypothesized that mechanical forces stimulate endothelial cells to secrete SMC chemoattractants to induce migration via the mitogen-activated protein kinase (MAPK) pathway. Methods: Bovine aortic endothelial cells were exposed to shear stress, cyclic strain, or static conditions for 16 hours. The resulting conditioned medium was used as a SMC chemoattractant in a Boyden chamber. Activation of SMC extracellular signal-regulated protein kinase 1/2 (ERK1/2) was assessed by Western blot analysis. Pathways were inhibited with anti-PDGF-BB or anti-interleukin-1α (IL-1α) antibodies, or the ERK1/2 upstream pathway inhibitor PD98059. Results: Conditioned medium from endothelial cells exposed to shear stress corresponding to arterial levels of shear stress stimulated SMC migration but lower levels of shear stress or cyclic strain did not. Both PDGF-BB and IL-1α were secreted into the conditioned medium by endothelial cells stimulated with shear stress. Both PDGF-BB and IL-1α stimulated SMC chemotaxis but were not synergistic, and both stimulated SMC ERK1/2 phosphorylation. Inhibition of PDGF-BB or IL-1α inhibited SMC chemotaxis and ERK1/2 phosphorylation. Conclusion: Shear stress stimulates endothelial cells to secrete several SMC chemoattractants, including PDGF-BB and IL-1α; both PDGF-BB and IL-1α stimulate SMC chemotaxis via the ERK1/2 signal-transduction pathway. These results suggest that the response to vascular injury may have a common pathway amenable to pharmacologic manipulation.
UR - http://www.scopus.com/inward/record.url?scp=14844291429&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=14844291429&partnerID=8YFLogxK
U2 - 10.1016/j.jvs.2004.11.016
DO - 10.1016/j.jvs.2004.11.016
M3 - Article
C2 - 15768016
AN - SCOPUS:14844291429
VL - 41
SP - 321
EP - 331
JO - Journal of Vascular Surgery
JF - Journal of Vascular Surgery
SN - 0741-5214
IS - 2
ER -