Date of Award

2007

Degree Name

Biological Sciences

College

College of Science

Type of Degree

M.S.

Document Type

Thesis

First Advisor

Eric R Blough

Second Advisor

David Mallory

Third Advisor

Simon Collier

Abstract

Vascular intervention procedures such as balloon angioplasty and stent implantation lead to denudation of endothelium exposing the underlying smooth muscle layer to effects of blood shear stress. The effect of shear stress on smooth muscle cell signaling has not been studied in depth. In this study, we examined time dependent changes in activation of Akt, mTOR and p70S6k related signaling in response to orbital shear stress on cultured A7r5 cells. A7r5 cells cultured to subconfluence on 150mm culture dishes were subjected to orbital shear of 9.8dynes/cm 2 for zero, 5 min, 15 min, 30 min, 1h, 4h and 24h. The cells were found to be reoriented with shear. Immunoblotting demonstrated increased phosphorylation of mTOR/p70s6krelated signaling proteins, suggesting an association between mTOR/p70s6k related signaling and shear induced reorientation of vascular smooth muscle cells. These data may provide insight into possible pharmacological interventions to prevent or retard the development of restenosis.

Subject(s)

Phosphorylation.

Vascular smooth muscle.

Vascular smooth muscle - Effect of drugs on.

Transluminal angioplasty.

Stents (Surgery).