Expression of Nuclear Lamin Proteins in Endothelial Cells is Sensitive to Cell Passage and Fluid Shear Stress

Vascular cells are regulated by continuous hemodynamic forces in vivo, and mechanical forces such as shear stress are proposed to involve in the progression of cardiovascular diseases such as atherosclerosis. Lamin A/C makes up the nuclear lamina, which structurally supports the nucleus while also functionally participates in chromatin organization and gene transcription. Diseases caused by lamin or other nuclear proteins are called laminopathies. One example, Hutchinson Gilford Progeria Syndrome (HGPS) where young patients show signs of accelerated aging, is caused by de novo mutations on the lamin A/C gene. Vasculature of HGPS patients shares many similarities with people of advanced age, suggesting a role for lamin in vascular aging.

In this study, we examined how arterial shear stress affects lamin A/C expression in bovine aortic endothelial cells at different population doubling levels (PDL). We also used fluorescence image analysis to examine nuclear shape changes with shear stress and PDL.

Our results suggest that laminar shear stress downregulated lamin A/C expression in low PDL cells, but the effect was reversed in high PDL cells. Nuclear shape changes were more prominent after shear stress in low PDL cells. Moreover, lamin A/C accumulated more at the nuclear periphery after exposure to shear stress.

Overall, our results indicate that both shear stress and cell passage can have an impact on lamin expressions at transcriptional and translational levels, as we continue to understand the effect of shear stress on endothelial lamina as part of the vascular aging process.