HDL in children with CKD promotes endothelial dysfunction and an abnormal vascular phenotype

Rukshana Shroff; Thimoteus Speer; Sophie Colin; Marietta Charakida; Stephen Zewinger; Bart Staels; Giulia Chinetti-Gbaguidi; Inga Hettrich; Lucia Rohrer; Francis O'Neill; Eve McLoughlin; David Long; Catherine M. Shanahan; Ulf Landmesser; Danilo Fliser; John E. Deanfield

doi:10.1681/ASN.2013111212

HDL in children with CKD promotes endothelial dysfunction and an abnormal vascular phenotype

Rukshana Shroff^*, Thimoteus Speer, Sophie Colin, Marietta Charakida, Stephen Zewinger, Bart Staels, Giulia Chinetti-Gbaguidi, Inga Hettrich, Lucia Rohrer, Francis O'Neill, Eve McLoughlin, David Long, Catherine M. Shanahan, Ulf Landmesser, Danilo Fliser, John E. Deanfield

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

103 Citations (Scopus)

Abstract

Endothelial dysfunction begins in early CKD and contributes to cardiovascular mortality. HDL is considered antiatherogenic, but may have adverse vascular effects in cardiovascular disease, diabetes, and inflammatory conditions. The effect of renal failure on HDL properties is unknown. We studied the endothelial effects of HDL isolated from 82 children with CKD stages 2-5 (HDL^CKD), who were free of underlying inflammatory diseases, diabetes, or active infections. Compared with HDL from healthy children, HDL^CKD strongly inhibited nitric oxide production, promoted superoxide production, and increased vascular cell adhesion molecule-1 expression in human aortic endothelial cells, and reduced cholesterol efflux from macrophages. The effects on endothelial cells correlated with CKD grade, with the most profound changes induced by HDL from patients on dialysis, and partial recovery observed with HDL isolated after kidney transplantation. Furthermore, the in vitro effects on endothelial cells associated with increased aortic pulse wave velocity, carotid intima-media thickness, and circulating markers of endothelial dysfunction in patients. Symmetric dimethylarginine levels were increased in serum and fractions of HDL from children with CKD. In a longitudinal follow-up of eight children undergoing kidney transplantation, HDL-induced production of endothelial nitric oxide, superoxide, and vascular cell adhesion molecule-1 in vitro improved significantly at 3 months after transplantation, but did not reach normal levels. These results suggest that in children with CKD without concomitant disease affecting HDL function, HDL dysfunction begins in early CKD, progressing as renal function declines, and is partially reversed after kidney transplantation.

Original language	English
Pages (from-to)	2658-2668
Number of pages	11
Journal	Journal of the American Society of Nephrology : JASN
Volume	25
Issue number	11
Early online date	22 May 2014
DOIs	https://doi.org/10.1681/ASN.2013111212
Publication status	Published - Nov 2014

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10.1681/ASN.2013111212

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Shroff, R., Speer, T., Colin, S., Charakida, M., Zewinger, S., Staels, B., Chinetti-Gbaguidi, G., Hettrich, I., Rohrer, L., O'Neill, F., McLoughlin, E., Long, D., Shanahan, C. M., Landmesser, U., Fliser, D., & Deanfield, J. E. (2014). HDL in children with CKD promotes endothelial dysfunction and an abnormal vascular phenotype. Journal of the American Society of Nephrology : JASN, 25(11), 2658-2668. https://doi.org/10.1681/ASN.2013111212

@article{f829aa901969430a905d28465153847b,

title = "HDL in children with CKD promotes endothelial dysfunction and an abnormal vascular phenotype",

abstract = "Endothelial dysfunction begins in early CKD and contributes to cardiovascular mortality. HDL is considered antiatherogenic, but may have adverse vascular effects in cardiovascular disease, diabetes, and inflammatory conditions. The effect of renal failure on HDL properties is unknown. We studied the endothelial effects of HDL isolated from 82 children with CKD stages 2-5 (HDLCKD), who were free of underlying inflammatory diseases, diabetes, or active infections. Compared with HDL from healthy children, HDLCKD strongly inhibited nitric oxide production, promoted superoxide production, and increased vascular cell adhesion molecule-1 expression in human aortic endothelial cells, and reduced cholesterol efflux from macrophages. The effects on endothelial cells correlated with CKD grade, with the most profound changes induced by HDL from patients on dialysis, and partial recovery observed with HDL isolated after kidney transplantation. Furthermore, the in vitro effects on endothelial cells associated with increased aortic pulse wave velocity, carotid intima-media thickness, and circulating markers of endothelial dysfunction in patients. Symmetric dimethylarginine levels were increased in serum and fractions of HDL from children with CKD. In a longitudinal follow-up of eight children undergoing kidney transplantation, HDL-induced production of endothelial nitric oxide, superoxide, and vascular cell adhesion molecule-1 in vitro improved significantly at 3 months after transplantation, but did not reach normal levels. These results suggest that in children with CKD without concomitant disease affecting HDL function, HDL dysfunction begins in early CKD, progressing as renal function declines, and is partially reversed after kidney transplantation.",

author = "Rukshana Shroff and Thimoteus Speer and Sophie Colin and Marietta Charakida and Stephen Zewinger and Bart Staels and Giulia Chinetti-Gbaguidi and Inga Hettrich and Lucia Rohrer and Francis O'Neill and Eve McLoughlin and David Long and Shanahan, {Catherine M.} and Ulf Landmesser and Danilo Fliser and Deanfield, {John E.}",

year = "2014",

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doi = "10.1681/ASN.2013111212",

language = "English",

volume = "25",

pages = "2658--2668",

journal = "Journal of the American Society of Nephrology : JASN",

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Shroff, R, Speer, T, Colin, S, Charakida, M, Zewinger, S, Staels, B, Chinetti-Gbaguidi, G, Hettrich, I, Rohrer, L, O'Neill, F, McLoughlin, E, Long, D, Shanahan, CM, Landmesser, U, Fliser, D & Deanfield, JE 2014, 'HDL in children with CKD promotes endothelial dysfunction and an abnormal vascular phenotype', Journal of the American Society of Nephrology : JASN, vol. 25, no. 11, pp. 2658-2668. https://doi.org/10.1681/ASN.2013111212

TY - JOUR

T1 - HDL in children with CKD promotes endothelial dysfunction and an abnormal vascular phenotype

AU - Shroff, Rukshana

AU - Speer, Thimoteus

AU - Colin, Sophie

AU - Charakida, Marietta

AU - Zewinger, Stephen

AU - Staels, Bart

AU - Chinetti-Gbaguidi, Giulia

AU - Hettrich, Inga

AU - Rohrer, Lucia

AU - O'Neill, Francis

AU - McLoughlin, Eve

AU - Long, David

AU - Shanahan, Catherine M.

AU - Landmesser, Ulf

AU - Fliser, Danilo

AU - Deanfield, John E.

PY - 2014/11

Y1 - 2014/11

N2 - Endothelial dysfunction begins in early CKD and contributes to cardiovascular mortality. HDL is considered antiatherogenic, but may have adverse vascular effects in cardiovascular disease, diabetes, and inflammatory conditions. The effect of renal failure on HDL properties is unknown. We studied the endothelial effects of HDL isolated from 82 children with CKD stages 2-5 (HDLCKD), who were free of underlying inflammatory diseases, diabetes, or active infections. Compared with HDL from healthy children, HDLCKD strongly inhibited nitric oxide production, promoted superoxide production, and increased vascular cell adhesion molecule-1 expression in human aortic endothelial cells, and reduced cholesterol efflux from macrophages. The effects on endothelial cells correlated with CKD grade, with the most profound changes induced by HDL from patients on dialysis, and partial recovery observed with HDL isolated after kidney transplantation. Furthermore, the in vitro effects on endothelial cells associated with increased aortic pulse wave velocity, carotid intima-media thickness, and circulating markers of endothelial dysfunction in patients. Symmetric dimethylarginine levels were increased in serum and fractions of HDL from children with CKD. In a longitudinal follow-up of eight children undergoing kidney transplantation, HDL-induced production of endothelial nitric oxide, superoxide, and vascular cell adhesion molecule-1 in vitro improved significantly at 3 months after transplantation, but did not reach normal levels. These results suggest that in children with CKD without concomitant disease affecting HDL function, HDL dysfunction begins in early CKD, progressing as renal function declines, and is partially reversed after kidney transplantation.

AB - Endothelial dysfunction begins in early CKD and contributes to cardiovascular mortality. HDL is considered antiatherogenic, but may have adverse vascular effects in cardiovascular disease, diabetes, and inflammatory conditions. The effect of renal failure on HDL properties is unknown. We studied the endothelial effects of HDL isolated from 82 children with CKD stages 2-5 (HDLCKD), who were free of underlying inflammatory diseases, diabetes, or active infections. Compared with HDL from healthy children, HDLCKD strongly inhibited nitric oxide production, promoted superoxide production, and increased vascular cell adhesion molecule-1 expression in human aortic endothelial cells, and reduced cholesterol efflux from macrophages. The effects on endothelial cells correlated with CKD grade, with the most profound changes induced by HDL from patients on dialysis, and partial recovery observed with HDL isolated after kidney transplantation. Furthermore, the in vitro effects on endothelial cells associated with increased aortic pulse wave velocity, carotid intima-media thickness, and circulating markers of endothelial dysfunction in patients. Symmetric dimethylarginine levels were increased in serum and fractions of HDL from children with CKD. In a longitudinal follow-up of eight children undergoing kidney transplantation, HDL-induced production of endothelial nitric oxide, superoxide, and vascular cell adhesion molecule-1 in vitro improved significantly at 3 months after transplantation, but did not reach normal levels. These results suggest that in children with CKD without concomitant disease affecting HDL function, HDL dysfunction begins in early CKD, progressing as renal function declines, and is partially reversed after kidney transplantation.

UR - http://www.scopus.com/inward/record.url?scp=84923945993&partnerID=8YFLogxK

U2 - 10.1681/ASN.2013111212

DO - 10.1681/ASN.2013111212

M3 - Article

C2 - 24854267

AN - SCOPUS:84923945993

SN - 1046-6673

VL - 25

SP - 2658

EP - 2668

JO - Journal of the American Society of Nephrology : JASN

JF - Journal of the American Society of Nephrology : JASN

IS - 11

ER -

HDL in children with CKD promotes endothelial dysfunction and an abnormal vascular phenotype

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