title: oxLDL-induced decrease in lipid order of membrane domains is inversely correlated with endothelial stiffness and network formation.
abstract: Oxidized low-density lipoprotein (oxLDL) is a major factor in development of atherosclerosis. Our earlier studies have shown that exposure of endothelial cells (EC) to oxLDL increases EC stiffness, facilitates the ability of the cells to generate force, and facilitates EC network formation in three-dimensional collagen gels. In this study, we show that oxLDL induces a decrease in lipid order of membrane domains and that this effect is inversely correlated with endothelial stiffness, contractility, and network formation. Local lipid packing of cell membrane domains was assessed by Laurdan two-photon imaging, endothelial stiffness was assessed by measuring cellular elastic modulus using atomic force microscopy, cell contractility was estimated by measuring the ability of the cells to contract collagen gels, and EC angiogenic potential was estimated by visualizing endothelial networks within the same gels. The impact of oxLDL on endothelial biomechanics and network formation is fully reversed by supplying the cells with a surplus of cholesterol. Furthermore, exposing the cells to 7-keto-cholesterol, a major oxysterol component of oxLDL, or to another cholesterol analog, androstenol, also results in disruption of lipid order of membrane domains and an increase in cell stiffness. On the basis of these observations, we suggest that disruption of lipid packing of cholesterol-rich membrane domains plays a key role in oxLDL-induced changes in endothelial biomechanics.
authors.affiliation: Pulmonary, Critical Care and Sleep Medicine, Dept. of Medicine, University of Illinois, Chicago, Illinois 60612-7323, USA.
authors.forename: Tzu Pin
authors.initials: TP
authors.lastname: Shentu
authors.forename: Igor
authors.initials: I
authors.lastname: Titushkin
authors.forename: Dev K
authors.initials: DK
authors.lastname: Singh
authors.forename: Keith J
authors.initials: KJ
authors.lastname: Gooch
authors.forename: Papasani V
authors.initials: PV
authors.lastname: Subbaiah
authors.forename: Michael
authors.initials: M
authors.lastname: Cho
authors.forename: Irena
authors.initials: I
authors.lastname: Levitan
mesh_terms: D000818:Animals; D050197:Atherosclerosis / Q000209:etiology / Q000473:pathology / Q000503:physiopathology; D001696:Biomechanical Phenomena / Q000502:physiology; D002417:Cattle; D002478:Cells, Cultured; D002784:Cholesterol / Q000737:chemistry / Q000378:metabolism / Q000502:physiology*; D004730:Endothelium, Vascular / Q000737:chemistry / Q000473:pathology / Q000503:physiopathology*; D008077:Lipoproteins, LDL / Q000737:chemistry / Q000502:physiology*; D021962:Membrane Microdomains / Q000737:chemistry / Q000473:pathology / Q000502:physiology*; D055806:Microvessels / Q000737:chemistry / Q000473:pathology / Q000503:physiopathology*; D009389:Neovascularization, Pathologic / Q000209:etiology / Q000473:pathology / Q000503:physiopathology
chemical_list: D008077:Lipoproteins, LDL; C099252:oxidized low density lipoprotein; D002784:Cholesterol
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