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VEGF-A Regulates Cellular Localization of SR-BI as Well as Transendothelial Transport of HDL but Not LDL.
Velagapudi, Srividya; Yalcinkaya, Mustafa; Piemontese, Antonio; Meier, Roger; Nørrelykke, Simon Flyvbjerg; Perisa, Damir; Rzepiela, Andrzej; Stebler, Michael; Stoma, Szymon; Zanoni, Paolo; Rohrer, Lucia; von Eckardstein, Arnold.
  • Velagapudi S; From the Institute of Clinical Chemistry, University and University Hospital of Zurich, Schlieren, Switzerland (S.V., M.Y., A.P., D.P., P.Z., L.R., A.v.E.); Competence Center for Integrated Human Physiology, University of Zurich, Switzerland (S.V., M.Y., D.P., P.Z., L.R., A.v.E.); Department of Phar
  • Yalcinkaya M; From the Institute of Clinical Chemistry, University and University Hospital of Zurich, Schlieren, Switzerland (S.V., M.Y., A.P., D.P., P.Z., L.R., A.v.E.); Competence Center for Integrated Human Physiology, University of Zurich, Switzerland (S.V., M.Y., D.P., P.Z., L.R., A.v.E.); Department of Phar
  • Piemontese A; From the Institute of Clinical Chemistry, University and University Hospital of Zurich, Schlieren, Switzerland (S.V., M.Y., A.P., D.P., P.Z., L.R., A.v.E.); Competence Center for Integrated Human Physiology, University of Zurich, Switzerland (S.V., M.Y., D.P., P.Z., L.R., A.v.E.); Department of Phar
  • Meier R; From the Institute of Clinical Chemistry, University and University Hospital of Zurich, Schlieren, Switzerland (S.V., M.Y., A.P., D.P., P.Z., L.R., A.v.E.); Competence Center for Integrated Human Physiology, University of Zurich, Switzerland (S.V., M.Y., D.P., P.Z., L.R., A.v.E.); Department of Phar
  • Nørrelykke SF; From the Institute of Clinical Chemistry, University and University Hospital of Zurich, Schlieren, Switzerland (S.V., M.Y., A.P., D.P., P.Z., L.R., A.v.E.); Competence Center for Integrated Human Physiology, University of Zurich, Switzerland (S.V., M.Y., D.P., P.Z., L.R., A.v.E.); Department of Phar
  • Perisa D; From the Institute of Clinical Chemistry, University and University Hospital of Zurich, Schlieren, Switzerland (S.V., M.Y., A.P., D.P., P.Z., L.R., A.v.E.); Competence Center for Integrated Human Physiology, University of Zurich, Switzerland (S.V., M.Y., D.P., P.Z., L.R., A.v.E.); Department of Phar
  • Rzepiela A; From the Institute of Clinical Chemistry, University and University Hospital of Zurich, Schlieren, Switzerland (S.V., M.Y., A.P., D.P., P.Z., L.R., A.v.E.); Competence Center for Integrated Human Physiology, University of Zurich, Switzerland (S.V., M.Y., D.P., P.Z., L.R., A.v.E.); Department of Phar
  • Stebler M; From the Institute of Clinical Chemistry, University and University Hospital of Zurich, Schlieren, Switzerland (S.V., M.Y., A.P., D.P., P.Z., L.R., A.v.E.); Competence Center for Integrated Human Physiology, University of Zurich, Switzerland (S.V., M.Y., D.P., P.Z., L.R., A.v.E.); Department of Phar
  • Stoma S; From the Institute of Clinical Chemistry, University and University Hospital of Zurich, Schlieren, Switzerland (S.V., M.Y., A.P., D.P., P.Z., L.R., A.v.E.); Competence Center for Integrated Human Physiology, University of Zurich, Switzerland (S.V., M.Y., D.P., P.Z., L.R., A.v.E.); Department of Phar
  • Zanoni P; From the Institute of Clinical Chemistry, University and University Hospital of Zurich, Schlieren, Switzerland (S.V., M.Y., A.P., D.P., P.Z., L.R., A.v.E.); Competence Center for Integrated Human Physiology, University of Zurich, Switzerland (S.V., M.Y., D.P., P.Z., L.R., A.v.E.); Department of Phar
  • Rohrer L; From the Institute of Clinical Chemistry, University and University Hospital of Zurich, Schlieren, Switzerland (S.V., M.Y., A.P., D.P., P.Z., L.R., A.v.E.); Competence Center for Integrated Human Physiology, University of Zurich, Switzerland (S.V., M.Y., D.P., P.Z., L.R., A.v.E.); Department of Phar
  • von Eckardstein A; From the Institute of Clinical Chemistry, University and University Hospital of Zurich, Schlieren, Switzerland (S.V., M.Y., A.P., D.P., P.Z., L.R., A.v.E.); Competence Center for Integrated Human Physiology, University of Zurich, Switzerland (S.V., M.Y., D.P., P.Z., L.R., A.v.E.); Department of Phar
Arterioscler Thromb Vasc Biol ; 37(5): 794-803, 2017 05.
Article en En | MEDLINE | ID: mdl-28360088
ABSTRACT

OBJECTIVE:

Low- and high-density lipoproteins (LDL and HDL) must pass the endothelial layer to exert pro- and antiatherogenic activities, respectively, within the vascular wall. However, the rate-limiting factors that mediate transendothelial transport of lipoproteins are yet little known. Therefore, we performed a high-throughput screen with kinase drug inhibitors to identify modulators of transendothelial LDL and HDL transport. APPROACH AND

RESULTS:

Microscopy-based high-content screening was performed by incubating human aortic endothelial cells with 141 kinase-inhibiting drugs and fluorescent-labeled LDL or HDL. Inhibitors of vascular endothelial growth factor (VEGF) receptors (VEGFR) significantly decreased the uptake of HDL but not LDL. Silencing of VEGF receptor 2 significantly decreased cellular binding, association, and transendothelial transport of 125I-HDL but not 125I-LDL. RNA interference with VEGF receptor 1 or VEGF receptor 3 had no effect. Binding, uptake, and transport of HDL but not LDL were strongly reduced in the absence of VEGF-A from the cell culture medium and were restored by the addition of VEGF-A. The restoring effect of VEGF-A on endothelial binding, uptake, and transport of HDL was abrogated by pharmacological inhibition of phosphatidyl-inositol 3 kinase/protein kinase B or p38 mitogen-activated protein kinase, as well as silencing of scavenger receptor BI. Moreover, the presence of VEGF-A was found to be a prerequisite for the localization of scavenger receptor BI in the plasma membrane of endothelial cells.

CONCLUSIONS:

The identification of VEGF as a regulatory factor of transendothelial transport of HDL but not LDL supports the concept that the endothelium is a specific and, hence, druggable barrier for the entry of lipoproteins into the vascular wall.
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Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Células Endoteliales / Factor A de Crecimiento Endotelial Vascular / Receptores Depuradores de Clase B / Lipoproteínas HDL / Lipoproteínas LDL Tipo de estudio: Prognostic_studies Límite: Humans Idioma: En Año: 2017 Tipo del documento: Article
Texto completo
Imprimir
XML
PubMed Links
Search on Google

Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Células Endoteliales / Factor A de Crecimiento Endotelial Vascular / Receptores Depuradores de Clase B / Lipoproteínas HDL / Lipoproteínas LDL Tipo de estudio: Prognostic_studies Límite: Humans Idioma: En Año: 2017 Tipo del documento: Article