ABSTRACT
It is now widely accepted that shear stress, a mechanical stimulus, regulates gene expression. There are a multitude of very good review papers covering this subject (Papadaki and Eskin, 1997, Resnick et al., 1995, Berk et al., 1995, Malek and Izumo, 1995, Malek and Izumo, 1994, Nollert et al., 1992). Signal pathways explaining how genes may be regulated by shear stress have been proposed in great detail and several shear stress regulatory elements have been identified. This chapter describes the effects of shear stress and other regulatory factors on gene expression in endothelial cells and how they compare with one another. This chapter also focuses attention on how mechanical and non-mechanical stimuli may interact with one another. To be able to intervene in the most intelligent way possible in biological systems we must understand how all parts of the system work in concert. We have chosen two general systems important in vascular biology as examples. The first is the immune/inflammation system in which the regulation of E-selectin, intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) and monocyte chemotactic protein-1 (MCP-1) are detailed. The second system we present involves the regulation of vascular tone and blood pressure. We cover C-type natriuretic peptide, (CNP), endothelin-1 (ET-1), angiotensin converting enzyme (ACE), prostaglandin H synthase (PGHS)-1 and PGHS-2. For each gene there is a description of its biological function, the effect of
shear stress on the expression of the gene and the effect of other stimuli on the gene’s expression. In many cases we have included time points and magnitudes of changes in gene expression to aide in the evaluation of the importance of the different stimuli and in how they may work together to regulate the different biological processes.
