Chronic pulsatile shear stress alters insulin-like growth factor-I (IGF-I) binding protein release in vitro

Insulin-like growth factor-I (IGF-I) is a potent smooth muscle cell mitogen indicated to have a role in vascular disease. IGF-I stimulates proliferation via receptor activation but its activity is mediated by IGF binding proteins (IGFBPs). Since hemodynamics have been linked to vascular proliferative disorders, we studied how pulsatile low (5 +/- 2 dynes/cm2) and high (23 +/- 8 dynes/cm2) shear stresses impacted IGFBP metabolism in bovine aortic endothelial cells using the Cellmax capillary system. We modeled the pulsatile flow in our system using the Womersley model for flow inside a rigid tube and harmonic analysis revealed that the flow was sinusoidal with a frequency of approximately 0.3 Hz for both shear stress treatments. Laminar flow was confirmed and the phase lag between the pressure and the flow found to be insignificant. Thus, our study provides a necessary characterization of this in vitro system as well as an investigation into how shear impacts the IGF axis. We found a significant difference in IGFBP distribution between treatments and, given that IGFBPs regulate IGF-I activity and that IGF-I-independent activities have been suggested for IGFBP-3, suggest that shear stress may indirectly regulate IGF-I activity, and, by extension, the effect of IGF-I on vascular pathologies.