title: Oscillatory shear stress increases smooth muscle cell proliferation and Akt phosphorylation.
abstract: OBJECTIVE
  Hemodynamic forces affect smooth muscle cell (SMC) proliferation and migration both in vitro and in vivo. However, the effects of oscillatory shear stress (SS) on SMC proliferation and signal transduction pathways that control survival are not well described.
  
  
  METHODS
  Bovine aortic SMC were exposed to arterial levels of oscillatory SS (14 dyne/cm(2)) with an orbital shaker; control cells were exposed to static conditions (0 dyne/cm(2)). Cell number and (3)[H]thymidine incorporation were measured after 1, 3, or 5 days of SS. Activation of the Akt pathway was assessed with the Western blot technique. Specificity of the phosphatidylinositol 3-kinase (PI3K) pathway was determined with the Western blot technique with the inhibitors LY294002 (10 micromol/L) or wortmannin (25 nmol/L).
  
  
  RESULTS
  Arterial levels of oscillatory SS increased SMC cell number by 20.1 +/- 3.7% and (3)[H]thymidine incorporation by 33.4% +/- 6.8% at 5 days. To identify whether SS increased activity of the SMC survival pathway, Akt activation was measured. SMC exposed to SS demonstrated increased Akt phosphorylation compared with control cells, with maximal phosphorylation at 60 minutes. Both PI3K inhibitors specifically inhibited the increase in Akt phosphorylation in SMC exposed to oscillatory SS.
  
  
  CONCLUSIONS
  SMC directly respond to oscillatory SS by increasing DNA synthesis, proliferation, and activation of the PI3K-Akt signal transduction pathway. These results suggest a mechanism of SMC survival and proliferation in response to endothelial-denuding arterial injury.
authors.affiliation: Department of Surgery, Section of Vascular Surgery, Yale University School of Medicine, 333 Cedar St, FMB 137, New Haven, CT 06520-8062, USA.
authors.forename: Masae
authors.initials: M
authors.lastname: Haga
authors.forename: Akimasa
authors.initials: A
authors.lastname: Yamashita
authors.forename: Jacek
authors.initials: J
authors.lastname: Paszkowiak
authors.forename: Bauer E
authors.initials: BE
authors.lastname: Sumpio
authors.forename: Alan
authors.initials: A
authors.lastname: Dardik
mesh_terms: D000818:Animals; D002417:Cattle; D002468:Cell Physiological Phenomena; D004195:Disease Models, Animal; D006439:Hemodynamics / Q000502:physiology; D066298:In Vitro Techniques; D032389:Myocytes, Smooth Muscle / Q000502:physiology*; D009991:Oscillometry; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000502:physiology*; D011518:Proto-Oncogene Proteins / Q000502:physiology*; D051057:Proto-Oncogene Proteins c-akt; D033081:Shear Strength; D015398:Signal Transduction / Q000502:physiology*; D013312:Stress, Physiological / Q000503:physiopathology*; D014652:Vascular Diseases / Q000503:physiopathology*
chemical_list: D019869:Phosphatidylinositol 3-Kinases; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D051057:Proto-Oncogene Proteins c-akt