Dysfunctional high-density lipoproteins in children with chronic kidney disease

Ryohei Kaseda, Kathy Jabs, Tracy E. Hunley, Deborah Jones, Aihua Bian, Ryan M. Allen, Kasey C. Vickers, Patricia G. Yancey, Macrae F. Linton, Sergio Fazio, Valentina Kon

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    38 Scopus citations

    Abstract

    Objectives. Our aim was to determine if chronic kidney disease (CKD) occurring in childhood impairs the normally vasoprotective functions of high-density lipoproteins (HDLs). Materials and methods. HDLs were isolated from children with end-stage renal disease on dialysis (ESRD), children with moderate CKD and controls with normal kidney function. Macrophage response to HDLs was studied as expression of inflammatory markers (MCP-1, TNF-α, IL-1β) and chemotaxis. Human umbilical vein endothelial cells were used for expression of adhesion molecules (ICAM-1, VCAM-1, E-selectin) and adhesion. Cellular proliferation, apoptosis, and necrosis of endothelial cells were measured by MTS/PMS reagent-based assay, flow cytometry, and ELISA. Cholesterol efflux was assessed by gas chromatographic measurements of cholesterol in macrophages exposed to HDLs. Results. Compared with HDLControl, HDLCKD and HDLESRD heightened the cytokine response and disrupted macrophage chemotaxis. HDLControl reduced endothelial expression of ICAM-1, VCAM-1, E-selectin, whereas HDLCKD and HDLESRD were less effective and showed reduced capacity to protect endothelial cells against monocyte adhesion. Compared with a dramatically enhanced endothelial proliferation following injurious stimulus by HDLControl, neither HDLCKD nor HDLESRD caused proliferative effects. HDLs of all three groups were equally protective against apoptosis assessed by flow cytometry and cleaved caspase-3 activity. Compared to HDLControl, HDLCKD and HDLESRD trended toward reduced capacity as cholesterol acceptors. Conclusion. CKD in children impairs HDL function. Even in the absence of long-standing and concomitant risk factors, CKD alters specific HDL functions linked to control of inflammation and endothelial responses.

    Original languageEnglish (US)
    Pages (from-to)263-273
    Number of pages11
    JournalMetabolism: Clinical and Experimental
    Volume64
    Issue number2
    DOIs
    StatePublished - Feb 1 2015

    Keywords

    • CKD
    • Child
    • Endothelial cell
    • HDL
    • Macrophage

    ASJC Scopus subject areas

    • Endocrinology, Diabetes and Metabolism
    • Endocrinology

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    Kaseda, R., Jabs, K., Hunley, T. E., Jones, D., Bian, A., Allen, R. M., Vickers, K. C., Yancey, P. G., Linton, M. F., Fazio, S., & Kon, V. (2015). Dysfunctional high-density lipoproteins in children with chronic kidney disease. Metabolism: Clinical and Experimental, 64(2), 263-273. https://doi.org/10.1016/j.metabol.2014.10.020