Figures & data
Figure 1. Schematic diagram showing the generation of shear stress (parallel to the endothelial cell surface) by blood flow and the generation of normal stress (perpendicular to the endothelial cell surface) and circumferential stretch due to the action of pressure. Reproduced with permission from Chien Citation11.
Figure 2. Schematic diagram showing the action of shear stress on potential sensors in endothelial cells (ECs), including receptor tyrosine kinases (RTK), G protein-coupled receptor (GPCR), ion channels, junction proteins, and integrins, as well as membrane lipids and glycocalyx. These mechanosensors act through adaptor molecules (represented by the two dotted circles) to activate upstream signaling molecules such as Ras, which then activate the mitogen-activated protein (MAP) kinase pathways, including ERK and JNK, and then the transcription factors (e.g. activator protein-1 (AP-1)) for gene expression (e.g. monocyte chemotactic protein-1 (MCP-1)). Arrows to the left of ERK and JNK are used to represent the phosphorylation cascade that involves the sequential phosphorylation of protein kinases one after the other. Various mechanotransduction pathways are used to modulate the expression of different genes. Also shown are the small GTPase Rho and its downstream molecules Rho kinase (ROCK) and mDia, which are stimulatory to actin. It is also possible for mechanical signals to be perceived by the cytoskeleton, including actin, to modulate gene expression, e.g. the interactions (direct or indirect) between actin and JNK. This diagram illustrates that mechanotransduction involves the interplay among many mechanosensors, signaling molecules, and genes, all of which form complex networks to modulate EC structure and function. Reproduced with permission from Chien Citation11.
Table I. Summary of effects of different flow patterns and associated shear stresses on EC and vascular biology.