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A triglyceride‐rich lipoprotein environment exacerbates renal injury in the accelerated nephrotoxic nephritis model

Hyperlipidaemia accompanies chronic renal disease either as a consequence of the renal dysfunction or as part of generalized metabolic derangements. Under both situations, the lipid profile is characterized by accumulation of triglyceride‐rich lipoproteins (TGRLs). This lipid profile is recognized a...

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Autores principales: Saja, M. F., Cook, H. T., Ruseva, M. M., Szajna, M., Pickering, M. C., Woollard, K. J., Botto, M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5980512/
https://www.ncbi.nlm.nih.gov/pubmed/29405270
http://dx.doi.org/10.1111/cei.13111
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author Saja, M. F.
Cook, H. T.
Ruseva, M. M.
Szajna, M.
Pickering, M. C.
Woollard, K. J.
Botto, M.
author_facet Saja, M. F.
Cook, H. T.
Ruseva, M. M.
Szajna, M.
Pickering, M. C.
Woollard, K. J.
Botto, M.
author_sort Saja, M. F.
collection PubMed
description Hyperlipidaemia accompanies chronic renal disease either as a consequence of the renal dysfunction or as part of generalized metabolic derangements. Under both situations, the lipid profile is characterized by accumulation of triglyceride‐rich lipoproteins (TGRLs). This lipid profile is recognized as a risk factor for cardiovascular complications. Whether it may pose a risk for renal injury as well remains unclear. A hyper‐TGRL state was generated in C57BL/6 mice using poloxamer‐407 (P‐407) and immune complex‐mediated renal injury was triggered using the accelerated nephrotoxic nephritis (ANTN) model. The hyper‐TGRL animals were hypersensitive to ANTN demonstrated by greater haematuria and glomerular cellularity. These changes were accompanied by increased glomerular accumulation of CD68(+) macrophages. The hypersensitive response to ANTN was not seen in low‐density lipoprotein receptor knock‐out mice fed with a high fat diet, where triglyceride levels were lower but cholesterol levels comparable to those obtained using P‐407. These data indicate that a hyper‐TGRL state might be more detrimental to the kidneys than low‐density lipoprotein‐driven hypercholesterolaemia during immune complex‐mediated nephritis. We speculate that the hyper‐TGRL environment primes the kidney to exacerbated renal damage following an inflammatory insult with increased accumulation of macrophages that may play a key role in mediating the injurious effects.
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spelling pubmed-59805122018-06-06 A triglyceride‐rich lipoprotein environment exacerbates renal injury in the accelerated nephrotoxic nephritis model Saja, M. F. Cook, H. T. Ruseva, M. M. Szajna, M. Pickering, M. C. Woollard, K. J. Botto, M. Clin Exp Immunol Original Articles Hyperlipidaemia accompanies chronic renal disease either as a consequence of the renal dysfunction or as part of generalized metabolic derangements. Under both situations, the lipid profile is characterized by accumulation of triglyceride‐rich lipoproteins (TGRLs). This lipid profile is recognized as a risk factor for cardiovascular complications. Whether it may pose a risk for renal injury as well remains unclear. A hyper‐TGRL state was generated in C57BL/6 mice using poloxamer‐407 (P‐407) and immune complex‐mediated renal injury was triggered using the accelerated nephrotoxic nephritis (ANTN) model. The hyper‐TGRL animals were hypersensitive to ANTN demonstrated by greater haematuria and glomerular cellularity. These changes were accompanied by increased glomerular accumulation of CD68(+) macrophages. The hypersensitive response to ANTN was not seen in low‐density lipoprotein receptor knock‐out mice fed with a high fat diet, where triglyceride levels were lower but cholesterol levels comparable to those obtained using P‐407. These data indicate that a hyper‐TGRL state might be more detrimental to the kidneys than low‐density lipoprotein‐driven hypercholesterolaemia during immune complex‐mediated nephritis. We speculate that the hyper‐TGRL environment primes the kidney to exacerbated renal damage following an inflammatory insult with increased accumulation of macrophages that may play a key role in mediating the injurious effects. John Wiley and Sons Inc. 2018-03-09 2018-06 /pmc/articles/PMC5980512/ /pubmed/29405270 http://dx.doi.org/10.1111/cei.13111 Text en © 2018 The Authors. Clinical & Experimental Immunology published by John Wiley & Sons Ltd on behalf of British Society for Immunology This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Articles
Saja, M. F.
Cook, H. T.
Ruseva, M. M.
Szajna, M.
Pickering, M. C.
Woollard, K. J.
Botto, M.
A triglyceride‐rich lipoprotein environment exacerbates renal injury in the accelerated nephrotoxic nephritis model
title A triglyceride‐rich lipoprotein environment exacerbates renal injury in the accelerated nephrotoxic nephritis model
title_full A triglyceride‐rich lipoprotein environment exacerbates renal injury in the accelerated nephrotoxic nephritis model
title_fullStr A triglyceride‐rich lipoprotein environment exacerbates renal injury in the accelerated nephrotoxic nephritis model
title_full_unstemmed A triglyceride‐rich lipoprotein environment exacerbates renal injury in the accelerated nephrotoxic nephritis model
title_short A triglyceride‐rich lipoprotein environment exacerbates renal injury in the accelerated nephrotoxic nephritis model
title_sort triglyceride‐rich lipoprotein environment exacerbates renal injury in the accelerated nephrotoxic nephritis model
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5980512/
https://www.ncbi.nlm.nih.gov/pubmed/29405270
http://dx.doi.org/10.1111/cei.13111
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