Shear stress-stimulated endothelial cells induce smooth muscle cell chemotaxis via platelet-derived growth factor-BB and interleukin-1α

Alan Dardik, Akimasa Yamashita, Faisal Aziz, Hidenori Asada, Bauer E. Sumpio

Research output: Contribution to journalArticlepeer-review

78 Scopus citations


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 languageEnglish (US)
Pages (from-to)321-331
Number of pages11
JournalJournal of Vascular Surgery
Issue number2
StatePublished - Feb 2005

All Science Journal Classification (ASJC) codes

  • Surgery
  • Cardiology and Cardiovascular Medicine


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