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L5, the most electronegative subfraction of plasma LDL, induces endothelial vascular cell adhesion molecule 1 and CXC chemokines, which mediate mononuclear leukocyte adhesion

  • Yasunori Abe
    Correspondence
    Corresponding author. Present address: Laboratories for Cardiovascular Research, Omiya Medical Center, Jichi Medical School 1-847 Amanuma-cho, Omiya-ku, Saitama-shi, Saitama-ken 330-8503, Japan. Tel.: +81 48 647 2111x5423; fax: +81 48 686 1015.
    Affiliations
    Section of Atherosclerosis and Lipoprotein Research, Department of Medicine, Baylor College of Medicine, 6565 Fannin, A679B, Houston, TX 77030, United States
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  • Myriam Fornage
    Affiliations
    Institute of Molecular Medicine, The University of Texas-Houston, Houston, TX 77030, United States
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  • Chao-yuh Yang
    Affiliations
    Section of Atherosclerosis and Lipoprotein Research, Department of Medicine, Baylor College of Medicine, 6565 Fannin, A679B, Houston, TX 77030, United States
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  • Ngoc-Anh Bui-Thanh
    Affiliations
    Section of Atherosclerosis and Lipoprotein Research, Department of Medicine, Baylor College of Medicine, 6565 Fannin, A679B, Houston, TX 77030, United States
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  • Vance Wise
    Affiliations
    Institute of Molecular Medicine, The University of Texas-Houston, Houston, TX 77030, United States
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  • Hsin-Hung Chen
    Affiliations
    Section of Atherosclerosis and Lipoprotein Research, Department of Medicine, Baylor College of Medicine, 6565 Fannin, A679B, Houston, TX 77030, United States
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  • Gopikishan Rangaraj
    Affiliations
    Section of Atherosclerosis and Lipoprotein Research, Department of Medicine, Baylor College of Medicine, 6565 Fannin, A679B, Houston, TX 77030, United States
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  • Christie M. Ballantyne
    Affiliations
    Section of Atherosclerosis and Lipoprotein Research, Department of Medicine, Baylor College of Medicine, 6565 Fannin, A679B, Houston, TX 77030, United States
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      Abstract

      We have previously reported that L5, the most negatively charged subfraction of plasma low-density lipoprotein (LDL), induces mononuclear leukocyte (MNC) adhesion under flow conditions in vitro when endothelial cells are incubated with L5. The present study was undertaken to identify responsible adhesion molecules and chemokines.
      LDL isolated from patients with homozygous familial hypercholesterolemia was separated into five distinct subfractions by high-capacity ion-exchange chromatography. Differentially expressed mRNA between human umbilical vein endothelial cells (HUVEC) incubated (for 22 h) with the earliest subfraction (L1: 20 μg/ml) and the latest and most negatively charged subfraction (L5: 20 μg/ml) was identified by DNA microarray analysis using three independent sets of RNA. mRNA consistently upregulated by L5 included VCAM-1 (2.3-fold) and CXC chemokines GRO-α (2.3), GRO-β (4.6), IL-8 (2.5), ENA-78 (2.3), GRO-γ (1.6) and GCP-2 (1.5). These results were validated by Northern analysis, semi-quantitative RT-PCR or ELISA.
      Blocking studies using monoclonal antibodies revealed that both primary capture and stable adhesion of MNC to HUVEC and human aortic endothelial cells (HAEC) incubated with L5 was mediated by VCAM-l/α4 integrin, whereas GRO and its receptor CXCR2 were involved in the stable adhesion of MNC to L5-treated HAEC.

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