Effect of Senescent Depletion of Nup93 in Endothelial Cells on Nuclear Shape and Size

Vascular aging, a chronic state of low-grade inflammation, is a known risk factor for cardiovascular diseases. As the innermost lining of the blood vasculature, endothelial cells (ECs) play a major role in vessel health. At the cellular level, appropriate nuclear structure determines proper cell functionality and homeostasis. Previous research identified nuclear pore complexes (NPCs) as crucial factors in maintaining nuclear integrity. Cell senescence has been shown to promote NPC degradation, leading to impaired nucleocytoplasmic transport. Age-induced loss of structural NPC component, nuceloporin93 (Nup93), in vascular endothelium increases pro- inflammatory signaling. However, the impact of NPC component degradation on the EC nuclear structure is undescribed. Due to Nup93’s role in NPC assembly, we hypothesized that targeted depletion of this protein would decrease nuclear size and disrupt its shape. To identify those changes, we employed a model of Nup93 depletion in endothelial cells, and through immunofluorescent visualization of the nuclear markers, we measured nuclear properties. Interestingly, loss of Nup93 in ECs increased nuclear size and decreased nuclear circularity, indicating the importance of proper nucleoporin expression in maintaining nuclear structure. Our findings signify the impact of Nup93 and cellular aging on nuclear shape and size, allowing to unearth more molecular mechanisms affecting nuclear structure.