Shear Stress Induced Release of PGI2 and PGE2 in Smooth Muscle Cells

Abstract Haemodynamic forces play an important role in regulating vessel wall structure and vascular tone. Shear stress is the fluid frictional force generated by the velocity gradient of fluid flow. The various cell types comprising the vascular wall experience shear stress through different mechanisms. The endothelium, being in direct contact with blood flow, experiences fluid shear forces which have been studied extensively. This shear stress for example, causes changes in the permeability of the endothelial cell layer (Jo et al., 1991). As a result, the fluid flow across the vascular wall increases exposing the underlying smooth muscle cell (SMC) layer directly to flow (and wall shear stress) driven by the transmural pressure gradient. The level of this wall shear stress sensed by the SMCs was calculated to be on the order of 1 dyne/cm2 (Wang D.M., & Tarbell J.M., in press). Shear stress levels of this magnitude are known to affect endothelial cells in vitro. Very little research has been done to study the relationship between shear stress and the arterial smooth muscle cell. We, therefore, decided to investigate whether SMCs can detect and respond to various levels of shear stress by measuring the release of the prostaglandins PGE2 and PGI2 (measured as its stable metabolite 6-keto-PGF1α) when subjected to various levels of shear stress. We chose these two types of prostaglandins because of their essential roles as vasodilators and regulators of vascular homeostasis. PGE2 and PGI2 have also been shown to decrease SMC proliferation rate (Pomerantz K., et al. 1989). Other studies have shown that increasing shear stress levels inhibits SMC proliferation, stimulates the synthesis of cell associated proteins, and regulates growth factor release (Sterpetti A.V. et al., 1992).