OxLDL and substrate stiffness promote neutrophil transmigration by enhanced endothelial cell contractility and ICAM-1.

Journal of Biomechanics
Kimberly M StrokaHelim Aranda-Espinoza

Abstract

Elevated levels of oxLDL in the bloodstream and increased vasculature stiffness are both associated with cardiovascular disease in patients. However, it is not known how oxLDL and subendothelial matrix stiffness together regulate an immune response. Here, we used an in vitro model of the vascular endothelium to explore the combined effects of oxLDL and subendothelial matrix stiffening on neutrophil transmigration. We prepared fibronectin-coated polyacrylamide gels of varying stiffness and plated human umbilical vein endothelial cells (ECs) onto the gels. We observed that oxLDL treatment of the endothelium promoted neutrophil transmigration (from <1% to 26% on soft 0.87kPa substrates), with stiffer substrates further promoting transmigration (54% on 5kPa and 41% on 280kPa). OxLDL exposure enhanced intercellular adhesion molecule-1 (ICAM-1) expression on the endothelium, which was likely responsible for the oxLDL-induced transmigration. Importantly, inhibition of MLCK-mediated EC contraction reduced transmigration to ∼9% on all substrates and eliminated the effects of subendothelial matrix stiffness. In addition, large holes, thousands of square microns in size, formed in monolayers on stiff substrates following transmigration, i...Continue Reading

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Citations

Mar 30, 2016·Journal of Biomechanics·Julie C KohnCynthia A Reinhart-King
Nov 28, 2012·Journal of Hepatology·Sofie M A WalenberghRonit Shiri-Sverdlov
Dec 3, 2015·Integrative Biology : Quantitative Biosciences From Nano to Macro·Joanna L MacKay, Daniel A Hammer
Sep 27, 2018·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Amanda S PelloweAnjelica L Gonzalez
Oct 18, 2013·American Journal of Physiology. Cell Physiology·Kimberly M Stroka, Konstantinos Konstantopoulos
Sep 15, 2017·Oncotarget·Kimberly M StrokaKonstantinos Konstantopoulos
Apr 8, 2015·The Journal of Immunology : Official Journal of the American Association of Immunologists·Michael Schnoor
Apr 18, 2019·Annals of Biomedical Engineering·Kelsey M GrayKimberly M Stroka
May 28, 2019·International Journal of Molecular Sciences·Shinsuke KikuchiTakahiro Ochiya
May 15, 2021·Frontiers in Immunology·Isaac M RichardsonLaurel E Hind

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