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
References
Jan 1, 1991·Research in Experimental Medicine. Zeitschrift Für Die Gesamte Experimentelle Medizin Einschliesslich Experimenteller Chirurgie·H A LehrK Messmer
Mar 1, 1995·Circulation·H A LehrK E Arfors
May 1, 1994·The Journal of Clinical Investigation·P F DaviesM L Griem
Jan 1, 1997·Free Radical Biology & Medicine·L CominaciniV Lo Cascio
Aug 7, 1997·The New England Journal of Medicine·M N DiazJ F Keaney
Oct 14, 1998·Circulation·P HolvoetD Collen
May 20, 1999·Hypertension·J BlacherM E Safar
Nov 5, 1999·The Journal of Biological Chemistry·A BlairE J Smart
Jan 4, 2001·Atherosclerosis·A TakeiM F Lopes-Virella
Nov 1, 2001·Trends in Cardiovascular Medicine·J A BerlinerD Vora
Jan 19, 2002·Hypertension·Pierre BoutouyrieStéphane Laurent
Mar 26, 2004·Biophysical Journal·Yan-Ting ShiuShu Chien
Sep 7, 2004·Biophysical Journal·Fitzroy J ByfieldIrena Levitan
Jan 19, 2006·Journal of Lipid Research·Fitzroy J ByfieldIrena Levitan
Aug 23, 2006·Cell·Adam J EnglerDennis E Discher
Dec 30, 2006·Atherosclerosis·Ken HashimotoFumihiko Kajiya
Jun 20, 2008·American Journal of Physiology. Cell Physiology·Gregory B KowalskyIrena Levitan
Aug 12, 2008·Experimental Cell Research·Julie A ChouinardPatrick Vermette
Apr 18, 2009·Cell Motility and the Cytoskeleton·Kimberly M Stroka, Helim Aranda-Espinoza
Nov 6, 2009·Antioxidants & Redox Signaling·Irena LevitanPapasani V Subbaiah
Feb 4, 2010·The FEBS Journal·Kimberly M Stroka, Helim Aranda-Espinoza
Sep 24, 2010·American Journal of Physiology. Cell Physiology·Ramaswamy KrishnanGeerten P van Nieuw Amerongen
Feb 4, 2011·Journal of Biomechanics·John PeloquinCynthia A Reinhart-King
Mar 2, 2011·Cellular and Molecular Bioengineering·Kimberly M Stroka, Helim Aranda-Espinoza
Apr 5, 2011·Cellular and Molecular Bioengineering·Leann L NormanHelim Aranda-Espinoza
Jun 10, 2011·Blood·Kimberly M Stroka, Helim Aranda-Espinoza
Citations
Apr 30, 2013·PloS One·Kimberly M StrokaHelim Aranda-Espinoza
Jul 11, 2013·PloS One·Gan ChenHong Zhou
Mar 30, 2016·Journal of Biomechanics·Julie C KohnCynthia A Reinhart-King
Dec 30, 2014·Cytoskeleton·Michael D OnkenJohn A Cooper
Nov 28, 2012·Journal of Hepatology·Sofie M A WalenberghRonit Shiri-Sverdlov
Mar 6, 2015·PloS One·István A KrizbaiAttila Sebe
Jan 6, 2016·PloS One·Jonas FranzChristoph Riethmüller
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
Oct 3, 2014·PloS One·Susan M HamillaHelim Aranda-Espinoza
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
Feb 8, 2019·Mediators of Inflammation·Xianfeng YanJilin Li
May 15, 2021·Frontiers in Immunology·Isaac M RichardsonLaurel E Hind
Oct 2, 2021·Experimental and Therapeutic Medicine·Qing LiJie Deng