LDL-Cholesterol Increases the Transcytosis of Molecules through Endothelial Monolayers

• Published in: PloS one 2016-10, Vol.11 (10), p.e0163988-e0163988
• Main Authors: Magalhaes, Ana, Matias, Inês, Palmela, Inês, Brito, Maria Alexandra, Dias, Sérgio
• Format: Article
• Language: English
• Subjects: Activation; Alzheimer's disease; Arteriosclerosis; Atherosclerosis; Biological Transport; Biology and Life Sciences; Blood cholesterol; Blood-brain barrier; Brain research; Cadherins; Cadherins - genetics; Cadherins - metabolism; Cancer; Capillary Permeability; Caveolae; Cell junctions; Cholesterol; Cholesterol, LDL - metabolism; Dextrans; Electrical junctions; Endothelial Cells - metabolism; Endothelium; Endothelium, Vascular - metabolism; Fluorescein; Gene Expression; Gene Silencing; Human Umbilical Vein Endothelial Cells; Humans; Immunoglobulins; Inflammation; Inflammatory response; Intercellular Junctions - metabolism; Laboratories; Lipids; Localization; Low density lipoprotein; Low density lipoproteins; Medicine and Health Sciences; Metastasis; Molecular weight; Monolayers; Monomolecular films; Pathological effects; Permeability; Physical Sciences; Proteins; Receptors, LDL - metabolism; Signal transduction; Signaling; Transcytosis; Zonula occludens-1 protein
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0163988

Cholesterol has been identified as a causative factor in numerous pathologies including atherosclerosis and cancer. One of the frequent effects of elevated cholesterol levels in humans is the compromise of endothelial function due to activation of pro-inflammatory signalling pathways. While the mechanisms involved in endothelial activation by cholesterol during an inflammatory response are well established, less is known about the mechanisms by which cholesterol may affect endothelial barrier function, which were the subject of the present study. Here we show that low density lipoprotein (LDL) increases the permeability of endothelial monolayers to high molecular weight dextrans in an LDL receptor and cholesterol-dependent manner. The increased permeability seen upon LDL treatment was not caused by disruption of cell-to-cell junctions as determined by a normal localization of VE-Cadherin and ZO-1 proteins, and no major alterations in transendothelial electrical resistance or permeability to fluorescein. We show instead that LDL increases the level of high molecular weight transcytosis and that this occurs in an LDL receptor, cholesterol and caveolae-dependent way. Our findings contribute to our understanding of the systemic pathological effects of elevated cholesterol and the transport of cargo through endothelial monolayers.