title: OxLDL increases endothelial stiffness, force generation, and network formation.
abstract: This study investigates the effect of oxidatively modified low density lipoprotein (OxLDL) on the biomechanical properties of human aortic endothelial cells (HAECs). We show that treatment with OxLDL results in a 90% decrease in the membrane deformability of HAECs, as determined by micropipette aspiration. Furthermore, aortic endothelial cells freshly isolated from hypercholesterolemic pigs were significantly stiffer than cells isolated from healthy animals. Interestingly, OxLDL had no effect on membrane cholesterol of HAECs but caused the disappearance of a lipid raft marker, GM1, from the plasma membrane. Both an increase in membrane stiffness and a disappearance of GM1 were also observed in cells that were cholesterol-depleted by methyl-beta-cyclodextrin. Additionally, OxLDL treatment of HAECs embedded within collagen gels resulted in increased gel contraction, indicating an increase in force generation by the cells. This increase in force generation correlated with an increased ability of HAECs to elongate and form networks in a three-dimensional environment. Increased force generation, elongation, and network formation were also observed in cholesterol-depleted cells. We suggest, therefore, that exposure to OxLDL results in the disruption or redistribution of lipid rafts, which in turn induces stiffening of the endothelium, an increase in endothelial force generation, and the potential for network formation.
authors.affiliation: Institute for Medicine and Engineering, Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Fitzroy J
authors.initials: FJ
authors.lastname: Byfield
authors.forename: Saloni
authors.initials: S
authors.lastname: Tikku
authors.forename: George H
authors.initials: GH
authors.lastname: Rothblat
authors.forename: Keith J
authors.initials: KJ
authors.lastname: Gooch
authors.forename: Irena
authors.initials: I
authors.lastname: Levitan
mesh_terms: D000818:Animals; D001011:Aorta / Q000166:cytology; D002462:Cell Membrane / Q000737:chemistry* / Q000378:metabolism; D002478:Cells, Cultured; D002784:Cholesterol / Q000378:metabolism; D042783:Endothelial Cells / Q000166:cytology / Q000378:metabolism*; D005677:G(M1) Ganglioside / Q000378:metabolism; D006801:Humans; D008077:Lipoproteins, LDL / Q000378:metabolism*; D019563:Mechanics; D018583:Pliability; D013552:Swine; D013718:Tensile Strength; D047392:beta-Cyclodextrins / Q000378:metabolism
chemical_list: D008077:Lipoproteins, LDL; D047392:beta-Cyclodextrins; C108732:methyl-beta-cyclodextrin; C099252:oxidized low density lipoprotein; D005677:G(M1) Ganglioside; D002784:Cholesterol