Identifying Mechanosensing Pathway Differences in Vein and Arterial Endothelial Cells

Coronary artery bypass graft (CABG) surgeries redirect blood flow from an obstruction in a vessel in order to maintain adequate blood flow within the cardiovascular system using a graft from the saphenous vein or radial artery. Five to seven years after a CABG procedure saphenous vein grafts have a success rate of 75-86%, whereas radial artery grafts have patencies of 90-98%. Reductions in vein success rate are due to thrombosis, intimal hyperplasia, and atherosclerosis. However, on a cellular level these changes could be initiated by sensors on endothelial cell surfaces that detect changes in shear stress experienced by the cell. Thus, we hypothesized that the differences between arterial and venous endothelial cell responses to fluid shear stress mediated by mechanosensors could contribute to earlier venous patency reduction in arterial settings. Using microfluidic devices to mimic blood flow we were able to show that vein endothelial cells do not respond to fluid shear stress as effectively as arterial endothelial cells. In addition, bulk RNA sequencing data shows that the upregulation of an ion channel known as Piezo2 could cause this decrease in sensitivity in vein endothelial cells. Furthermore, knockdown and knockout of PIEZO2 in vein endothelial cells did show increased sensitivity to shear stress. The results of this study show that vein endothelial cells do not have the same mechanosensitive abilities as arterial endothelial cells; however, mechanosensitive function can be rescued by PIEZO2 knockdown. These insights could potentially be crucial in synthesizing vessel grafts that are resistant to adverse vascular pathologies thus leading to better long term outcomes for CABG and vascular disease patients.