Cargando…

Enhanced protection of the renal vascular endothelium improves early outcome in kidney transplantation: Preclinical investigations in pig and mouse

Ischemia reperfusion injury is one of the major complications responsible for delayed graft function in kidney transplantation. Applications to reduce reperfusion injury are essential due to the widespread use of kidneys from deceased organ donors where the risk for delayed graft function is especia...

Descripción completa

Detalles Bibliográficos
Autores principales: Nordling, Sofia, Brännström, Johan, Carlsson, Fredrik, Lu, Bo, Salvaris, Evelyn, Wanders, Alkwin, Buijs, Jos, Estrada, Sergio, Tolmachev, Vladimir, Cowan, Peter J., Lorant, Tomas, Magnusson, Peetra U.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5979943/
https://www.ncbi.nlm.nih.gov/pubmed/29581529
http://dx.doi.org/10.1038/s41598-018-21463-1
_version_ 1783327794875334656
author Nordling, Sofia
Brännström, Johan
Carlsson, Fredrik
Lu, Bo
Salvaris, Evelyn
Wanders, Alkwin
Buijs, Jos
Estrada, Sergio
Tolmachev, Vladimir
Cowan, Peter J.
Lorant, Tomas
Magnusson, Peetra U.
author_facet Nordling, Sofia
Brännström, Johan
Carlsson, Fredrik
Lu, Bo
Salvaris, Evelyn
Wanders, Alkwin
Buijs, Jos
Estrada, Sergio
Tolmachev, Vladimir
Cowan, Peter J.
Lorant, Tomas
Magnusson, Peetra U.
author_sort Nordling, Sofia
collection PubMed
description Ischemia reperfusion injury is one of the major complications responsible for delayed graft function in kidney transplantation. Applications to reduce reperfusion injury are essential due to the widespread use of kidneys from deceased organ donors where the risk for delayed graft function is especially prominent. We have recently shown that coating of inflamed or damaged endothelial cells with a unique heparin conjugate reduces thrombosis and leukocyte recruitment. In this study we evaluated the binding capacity of the heparin conjugate to cultured human endothelial cells, to kidneys from brain-dead porcine donors, and to murine kidneys during static cold storage. The heparin conjugate was able to stably bind cultured endothelial cells with high avidity, and to the renal vasculature of explanted kidneys from pigs and mice. Treatment of murine kidneys prior to transplantation reduced platelet deposition and leukocyte infiltration 24 hours post-transplantation, and significantly improved graft function. The present study thus shows the benefits of enhanced protection of the renal vasculature during cold storage, whereby increasing the antithrombotic and anti-adhesive properties of the vascular endothelium yields improved renal function early after transplantation.
format Online
Article
Text
id pubmed-5979943
institution National Center for Biotechnology Information
language English
publishDate 2018
publisher Nature Publishing Group UK
record_format MEDLINE/PubMed
spelling pubmed-59799432018-06-06 Enhanced protection of the renal vascular endothelium improves early outcome in kidney transplantation: Preclinical investigations in pig and mouse Nordling, Sofia Brännström, Johan Carlsson, Fredrik Lu, Bo Salvaris, Evelyn Wanders, Alkwin Buijs, Jos Estrada, Sergio Tolmachev, Vladimir Cowan, Peter J. Lorant, Tomas Magnusson, Peetra U. Sci Rep Article Ischemia reperfusion injury is one of the major complications responsible for delayed graft function in kidney transplantation. Applications to reduce reperfusion injury are essential due to the widespread use of kidneys from deceased organ donors where the risk for delayed graft function is especially prominent. We have recently shown that coating of inflamed or damaged endothelial cells with a unique heparin conjugate reduces thrombosis and leukocyte recruitment. In this study we evaluated the binding capacity of the heparin conjugate to cultured human endothelial cells, to kidneys from brain-dead porcine donors, and to murine kidneys during static cold storage. The heparin conjugate was able to stably bind cultured endothelial cells with high avidity, and to the renal vasculature of explanted kidneys from pigs and mice. Treatment of murine kidneys prior to transplantation reduced platelet deposition and leukocyte infiltration 24 hours post-transplantation, and significantly improved graft function. The present study thus shows the benefits of enhanced protection of the renal vasculature during cold storage, whereby increasing the antithrombotic and anti-adhesive properties of the vascular endothelium yields improved renal function early after transplantation. Nature Publishing Group UK 2018-03-26 /pmc/articles/PMC5979943/ /pubmed/29581529 http://dx.doi.org/10.1038/s41598-018-21463-1 Text en © The Author(s) 2018 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Nordling, Sofia
Brännström, Johan
Carlsson, Fredrik
Lu, Bo
Salvaris, Evelyn
Wanders, Alkwin
Buijs, Jos
Estrada, Sergio
Tolmachev, Vladimir
Cowan, Peter J.
Lorant, Tomas
Magnusson, Peetra U.
Enhanced protection of the renal vascular endothelium improves early outcome in kidney transplantation: Preclinical investigations in pig and mouse
title Enhanced protection of the renal vascular endothelium improves early outcome in kidney transplantation: Preclinical investigations in pig and mouse
title_full Enhanced protection of the renal vascular endothelium improves early outcome in kidney transplantation: Preclinical investigations in pig and mouse
title_fullStr Enhanced protection of the renal vascular endothelium improves early outcome in kidney transplantation: Preclinical investigations in pig and mouse
title_full_unstemmed Enhanced protection of the renal vascular endothelium improves early outcome in kidney transplantation: Preclinical investigations in pig and mouse
title_short Enhanced protection of the renal vascular endothelium improves early outcome in kidney transplantation: Preclinical investigations in pig and mouse
title_sort enhanced protection of the renal vascular endothelium improves early outcome in kidney transplantation: preclinical investigations in pig and mouse
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5979943/
https://www.ncbi.nlm.nih.gov/pubmed/29581529
http://dx.doi.org/10.1038/s41598-018-21463-1
work_keys_str_mv AT nordlingsofia enhancedprotectionoftherenalvascularendotheliumimprovesearlyoutcomeinkidneytransplantationpreclinicalinvestigationsinpigandmouse
AT brannstromjohan enhancedprotectionoftherenalvascularendotheliumimprovesearlyoutcomeinkidneytransplantationpreclinicalinvestigationsinpigandmouse
AT carlssonfredrik enhancedprotectionoftherenalvascularendotheliumimprovesearlyoutcomeinkidneytransplantationpreclinicalinvestigationsinpigandmouse
AT lubo enhancedprotectionoftherenalvascularendotheliumimprovesearlyoutcomeinkidneytransplantationpreclinicalinvestigationsinpigandmouse
AT salvarisevelyn enhancedprotectionoftherenalvascularendotheliumimprovesearlyoutcomeinkidneytransplantationpreclinicalinvestigationsinpigandmouse
AT wandersalkwin enhancedprotectionoftherenalvascularendotheliumimprovesearlyoutcomeinkidneytransplantationpreclinicalinvestigationsinpigandmouse
AT buijsjos enhancedprotectionoftherenalvascularendotheliumimprovesearlyoutcomeinkidneytransplantationpreclinicalinvestigationsinpigandmouse
AT estradasergio enhancedprotectionoftherenalvascularendotheliumimprovesearlyoutcomeinkidneytransplantationpreclinicalinvestigationsinpigandmouse
AT tolmachevvladimir enhancedprotectionoftherenalvascularendotheliumimprovesearlyoutcomeinkidneytransplantationpreclinicalinvestigationsinpigandmouse
AT cowanpeterj enhancedprotectionoftherenalvascularendotheliumimprovesearlyoutcomeinkidneytransplantationpreclinicalinvestigationsinpigandmouse
AT loranttomas enhancedprotectionoftherenalvascularendotheliumimprovesearlyoutcomeinkidneytransplantationpreclinicalinvestigationsinpigandmouse
AT magnussonpeetrau enhancedprotectionoftherenalvascularendotheliumimprovesearlyoutcomeinkidneytransplantationpreclinicalinvestigationsinpigandmouse