Endothelial Nuclear and Cytoskeletal Responses to Mechanical Stresses.

摘要

The ability of vascular endothelium to sense and respond to the mechanical stimuli generated by blood flow is pivotal in maintaining arterial homeostasis. A steady laminar flow tends to provide atheroprotective effect via regulating endothelial functions, vascular tone, and further remodeling process. The occurrence of cardiovascular diseases increases with age, and the percentage of senescent cells is significantly elevated in vascular cells at atherosclerotic sites. As arterial aging appeared to be an independent risk factor for cardiovascular diseases, it is critical to understand the effects of cell senescence on endothelial dysfunction under dynamic mechanical stimuli. We found that shear stress-induced actin alignment in flow direction was more dependent on cell passages than on cyclic strain. For high passage cells, the mean angle was shifted toward the shear direction by 6.9 degrees more than the control. Similarly, nuclear orientation in endothelial cells shifted toward the flow direction by 9 degrees on average for cells at higher passage. Our results demonstrated similar trends between actin and nuclear structural adaptation to mechanical stresses in response. The failure of higher PDL endothelial cells to adapt morphologically to applied shear stress could be one of the contributors to endothelial dysfunctions during vascular aging. Overall, our results indicate that both shear stress and cell passage can have an impact on lamin expressions on transcriptional and translational levels, as we continue to understand the effect of shear stress on endothelial lamina as part of the vascular aging process.