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

    Research output: Contribution to journalArticle

    33 Citations (Scopus)

    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

    Fingerprint

    HDL Lipoproteins
    Chronic Renal Insufficiency
    E-Selectin
    Vascular Cell Adhesion Molecule-1
    Macrophages
    Cholesterol
    Chemotaxis
    Intercellular Adhesion Molecule-1
    Flow Cytometry
    Endothelial Cells
    Apoptosis
    Human Umbilical Vein Endothelial Cells
    Interleukin-1
    Caspase 3
    Chronic Kidney Failure
    Dialysis
    Monocytes
    Necrosis
    Gases
    Enzyme-Linked Immunosorbent Assay

    Keywords

    • Child
    • CKD
    • Endothelial cell
    • HDL
    • Macrophage

    ASJC Scopus subject areas

    • Endocrinology
    • Endocrinology, Diabetes and Metabolism

    Cite this

    Kaseda, R., Jabs, K., Hunley, T. E., Jones, D., Bian, A., Allen, R. M., ... 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

    Dysfunctional high-density lipoproteins in children with chronic kidney disease. / Kaseda, Ryohei; Jabs, Kathy; Hunley, Tracy E.; Jones, Deborah; Bian, Aihua; Allen, Ryan M.; Vickers, Kasey C.; Yancey, Patricia G.; Linton, Macrae F.; Fazio, Sergio; Kon, Valentina.

    In: Metabolism: Clinical and Experimental, Vol. 64, No. 2, 01.02.2015, p. 263-273.

    Research output: Contribution to journalArticle

    Kaseda, R, Jabs, K, Hunley, TE, Jones, D, Bian, A, Allen, RM, Vickers, KC, Yancey, PG, Linton, MF, Fazio, S & Kon, V 2015, 'Dysfunctional high-density lipoproteins in children with chronic kidney disease', Metabolism: Clinical and Experimental, vol. 64, no. 2, pp. 263-273. https://doi.org/10.1016/j.metabol.2014.10.020
    Kaseda, Ryohei ; Jabs, Kathy ; Hunley, Tracy E. ; Jones, Deborah ; Bian, Aihua ; Allen, Ryan M. ; Vickers, Kasey C. ; Yancey, Patricia G. ; Linton, Macrae F. ; Fazio, Sergio ; Kon, Valentina. / Dysfunctional high-density lipoproteins in children with chronic kidney disease. In: Metabolism: Clinical and Experimental. 2015 ; Vol. 64, No. 2. pp. 263-273.
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    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.",
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    AU - Jabs, Kathy

    AU - Hunley, Tracy E.

    AU - Jones, Deborah

    AU - Bian, Aihua

    AU - Allen, Ryan M.

    AU - Vickers, Kasey C.

    AU - Yancey, Patricia G.

    AU - Linton, Macrae F.

    AU - Fazio, Sergio

    AU - Kon, Valentina

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    N2 - 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.

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