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

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