Extracellular histone H3: biomarker and therapeutic target for the prevention of tissue damage

Daniëlle M.H. Beurskens

doi:10.26481/dis.20200320db

Extracellular histone H3: biomarker and therapeutic target for the prevention of tissue damage

Daniëlle M.H. Beurskens

Research output: Thesis › Doctoral Thesis › Internal

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Abstract

This research was aimed at studying histone proteins in tissue damage. An important finding was that the more histones were present in donor kidneys during machine preservation, the poorer the organ function after transplantation. The amount of histones seems to be related to the amount of kidney damage. Heparin, which can neutralize histones, was found to have no influence on the amount of histones or damage in donor kidneys. Further research will have to look into optimization of organ preservation.
The neutralization of histones with the APC protein was also investigated. For this, APC variants were designed that were predicted to bind histones better than normal APC. These new variants neutralize histones, but were no better than normal APC. The exact effectiveness and possible improvements of these APC variants still need to be investigated.

Original language	English
Awarding Institution	Maastricht University
Supervisors/Advisors	Reutelingsperger, Christiaan, Supervisor Nicolaes, Gerry, Co-Supervisor
Award date	2 Jul 2020
Place of Publication	Maastricht
Publisher	Ridderprint
Print ISBNs	9789463754255
DOIs	https://doi.org/10.26481/dis.20200320db
Publication status	Published - 2020

Keywords

extracellular histones
tissue damage
sepsis
kidney donation
microcirculation

Access to Document

10.26481/dis.20200320db

Full TextFinal published version, 7.62 MB
AbstractFinal published version, 211 KB
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ValorisationFinal published version, 185 KB

Cite this

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title = "Extracellular histone H3: biomarker and therapeutic target for the prevention of tissue damage",

abstract = "This research was aimed at studying histone proteins in tissue damage. An important finding was that the more histones were present in donor kidneys during machine preservation, the poorer the organ function after transplantation. The amount of histones seems to be related to the amount of kidney damage. Heparin, which can neutralize histones, was found to have no influence on the amount of histones or damage in donor kidneys. Further research will have to look into optimization of organ preservation.The neutralization of histones with the APC protein was also investigated. For this, APC variants were designed that were predicted to bind histones better than normal APC. These new variants neutralize histones, but were no better than normal APC. The exact effectiveness and possible improvements of these APC variants still need to be investigated.",

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AB - This research was aimed at studying histone proteins in tissue damage. An important finding was that the more histones were present in donor kidneys during machine preservation, the poorer the organ function after transplantation. The amount of histones seems to be related to the amount of kidney damage. Heparin, which can neutralize histones, was found to have no influence on the amount of histones or damage in donor kidneys. Further research will have to look into optimization of organ preservation.The neutralization of histones with the APC protein was also investigated. For this, APC variants were designed that were predicted to bind histones better than normal APC. These new variants neutralize histones, but were no better than normal APC. The exact effectiveness and possible improvements of these APC variants still need to be investigated.

KW - extracellular histones

KW - tissue damage

KW - sepsis

KW - kidney donation

KW - microcirculation

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