Mechanisms of Mechanochemical Transduction in Vascular Cells

Summary

Mechanical stimuli can modulate vascular functions by activating sequentially the mechanosensors, intracellular signaling pathways, specific transcription factors, and gene and protein expressions. We found that receptor tyrosine kinases on the luminal side of endothelial cells (ECs) and integrins on the abluminal side can serve as mechanosensors. The activation of these mechanosensors leads to the phosphorylation cascade of signaling molecules. For example, the Ras-MEKK-JNK signaling pathway mediates the transient MCP-1 expression induced by laminar shear stress. Long-term laminar shear stress downregulates MCP-1 and activates other genes, including those causing cell cycle arrest. This may provide a molecular basis for the anti-atherogenic function of long-term laminar shear stress in the straight part of the arterial tree. The complex flow pattern in branch points, including the flow reattachment area that has a low shear stress and a high shear stress gradient, was simulated in a step-flow channel. In the flow reattachment area, the atherogenic genes are not downregulated, and EC mitosis and apoptosis are accelerated, contributing to the preferential localization of atherosclerosis at branch points. The effects of mechanical stimuli on signal transduction and gene expression play significant roles in the regulation of vascular functions in health and disease.