Heparanase Inhibition Preserves the Endothelial Glycocalyx in Lung Grafts and Improves Lung Preservation and Transplant Outcomes

A research team including cardiothoracic, pulmonary, and cell biology and physiology experts from the University of Pittsburgh conducted a study that examined the effect of endothelial glycocalyx (eGC) protection through heparanase inhibition on lung graft quality. 

The protection of the eGC is important in determining the overall success of transplants, as this layer of the blood vessel aids in the prevention of vascular injury and disease. If the eGC is deteriorated, post-transplant results can become compromised due to poor graft quality, graft dysfunction, and cellular rejection. 

This study examined four groups of rat lung models that had either damaged eGC or preserved eGC. Group 1 contained rats with native lungs and functioned as the normal control group. Group 2 contained rats with lungs that had significant eGC damage, which functioned as a second control group. Group 3 contained rats with lungs in which eGC was preserved by heparin, and Group 4 contained rats with lungs in which eGC was preserved by N-acetyl heparin (NAH).

Groups 2, 3, and 4 were exposed to 1 hour of ischemic insult, also known as a restriction in blood supply, and were then subjected to either direct lung transplantation or to ex vivo lung perfusion (EVLP).

Transmission electron microscopy (TEM) was used to assess changes in eGC after the ischemic insult. In Group 2, the eGC shed significantly and became completely detached in several regions due to high heparanase activation. 

Contrastingly, the eGC did not shed in Group 3 and Group 4, groups that were treated with either heparin or NAH, respectively, prior to ischemic insult. Therefore, heparanase activation was inhibited, causing eGC to remain preserved and free of vascular damage.

Study results demonstrate that damaged eGC increases the risk of graft failure after transplantation. Results also demonstrated that preservation of the eGC through heparanase inhibition can attenuate lung injury and improve both graft function and quality. 

Ultimately, the findings from this study reinforce the importance of the endothelial glycocalyx in protecting the lung graft from ischemic injury and highlight a novel therapeutic means to preserve the glycocalyx, thereby promoting improved post-transplant outcomes.

Read the full study here.

Reference 

Noda K, Philips BJ, Snyder ME, et al. Heparanase inhibition preserves the endothelial glycocalyx in lung grafts and improves lung preservation and transplant outcomes. Sci Rep. 2021;11(1):12265. Published 2021 Jun 10. doi:10.1038/s41598-021-91777-0