UC San Diego

In physiological shock, a leading cause of death, cell and tissue function are compromised. Once proteases enter into the circulation during shock, there may be proteolytic damage to the extracellular components of cells including cleavage of surface receptors and the glycocalyx of the endothelial cells (ECs). The endothelial cell is sensitive to physiological shear stress (typically 10-15 dyn/cm²) and aligns in the direction of the fluid flow. Sheared endothelial cells exhibited a higher tolerance to protease exposure than static cells. Extracellular damage to the endothelial cell by active proteases causes the ECs to not align in the direction of the fluid shear stress; however when the proteases were inhibited, ECs exposed to shear stress could realign with the direction of the flow. Receptor intensity of the mechanosensors VEGFR-2 and junctional PECAM-1 was reduced on both sheared and unsheared ECs. The insulin receptor surface density was also reduced for cells exposed to proteases. In conclusion, proteases present in the circulation during shock may damage extracellular molecular membrane components on the cell and interfere with one of the most basic mechanotransduction mechanisms in endothelial cells, i.e. aligning in the presence of physiological shear stress