Dysfunctional high-density lipoproteins in children with chronic kidney disease.

Kaseda R, Jabs K, Hunley TE, Jones D, Bian A, Allen RM, Vickers KC, Yancey PG, Linton MF, Fazio S, Kon V
Metabolism. 2015 64 (2): 263-73

PMID: 25467845 · PMCID: PMC4277938 · DOI:10.1016/j.metabol.2014.10.020

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 HDL(Control), HDL(CKD) and HDL(ESRD) heightened the cytokine response and disrupted macrophage chemotaxis. HDL(Control) reduced endothelial expression of ICAM-1, VCAM-1, E-selectin, whereas HDL(CKD) and HDL(ESRD) 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 HDL(Control), neither HDL(CKD) nor HDL(ESRD) caused proliferative effects. HDLs of all three groups were equally protective against apoptosis assessed by flow cytometry and cleaved caspase-3 activity. Compared to HDL(Control), HDL(CKD) and HDL(ESRD) 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.

Copyright © 2015 Elsevier Inc. All rights reserved.

MeSH Terms (24)

Adolescent Apoptosis Biological Transport Cardiovascular Diseases Cell Adhesion Cell Line Cell Proliferation Cells, Cultured Chemotaxis Child Child, Preschool Cholesterol Coculture Techniques Endothelium, Vascular Humans Human Umbilical Vein Endothelial Cells Infant Kidney Failure, Chronic Lipoproteins, HDL Macrophages Renal Insufficiency, Chronic Risk Factors Severity of Illness Index Tennessee

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