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Endothelial Nuclear Lamina in Mechanotransduction Under Shear Stress

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Molecular, Cellular, and Tissue Engineering of the Vascular System

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 1097))

Abstract

Endothelial cells that line the lumen of blood vessels are at the interface between hemodynamic forces and vascular wall biology. Endothelial cells transduce mechanical and biological signals from blood flow into intracellular signaling cascades through a process called mechanotransduction. Mechanotransduction is an important part of normal cell functions, as well as endothelial dysfunction which leads to inflammation and pathological conditions. For example, atherosclerosis preferentially develops in regions of disturbed fluid flow and low shear stress. The nuclear lamina, which sits underneath the nuclear envelope, serves to maintain the nuclear structure while acting as a scaffold for heterochromatin and many transcriptional proteins. Defects in lamina and its associated proteins cause a variety of human diseases including accelerated aging diseases such as Hutchinson-Gilford Progeria syndrome. The role of nuclear lamina in endothelial mechanotransduction, specifically how nuclear mechanics impact gene regulation under shear stress, is not fully understood. In one study, lamin A/C was silenced in bovine aortic endothelial cells to determine its role in both glucocorticoid receptor (GR) nuclear translocation and glucocorticoid response element (GRE) transcriptional activation in response to its natural ligand dexamethasone as well as fluid shear stress. Results suggest that absence of lamin A/C does not hinder passage of GR into the nucleus but nuclear lamina is important to properly regulate GRE transcription. Ongoing research continues to investigate how nuclear lamins contribute to endothelial mechanotransduction and to better understand the role of Lamin A in vascular aging and in the progression of cardiovascular diseases.

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  1. Department of Biomedical Engineering, Indiana University Purdue University Indianapolis, Indianapolis, IN, USA

    Julie Y. Ji

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  1. Department of Biomedical Engineering, The City College of the City University of New York, New York, NY, USA

    Bingmei M. Fu

  2. Department of Mechanical Engineering, Michigan State University, East Lansing, MI, USA

    Neil T. Wright

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Ji, J.Y. (2018). Endothelial Nuclear Lamina in Mechanotransduction Under Shear Stress. In: Fu, B., Wright, N. (eds) Molecular, Cellular, and Tissue Engineering of the Vascular System. Advances in Experimental Medicine and Biology, vol 1097. Springer, Cham. https://doi.org/10.1007/978-3-319-96445-4_5

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