Acute injury to the endothelium and its protective glycocalyx layer

: preventative therapies for organ transplantation

Abstract

The endothelial glycocalyx (EG) acts as a barrier between circulating blood and the vessel wall. Composed of proteoglycans (PGs), glycosaminoglycans (GAGs), and glycoproteins, it covers the luminal layer of endothelial cells, and its dynamic structure plays a crucial role in endothelial functions and vascular pathophysiology. Research has shown that its degradation has significant pathological effects on human health, underscoring the importance of maintaining its integrity. Brain death (BD) has been found to induce EG alteration by exacerbating ischemia-reperfusion injury and inflammation during organ transplantation. Consequently, BD and the resulting EG degradation increase the risk of graft failure following transplantation. Studies have also indicated that EG degradation prior to and during transplantation serves as a risk factor for graft failure. Hence, it has become customary to explore ways of preserving or restoring EG to enhance graft survival. To enhance the post-transplantation function of grafts, various crucial stages throughout the organ transplantation process can be addressed. These stages include BD, organ procurement, organ preservation, organ transplantation, and posttransplantation care. This review aims to provide an overview of current preventive options that have been highlighted to have an impact on EG integrity, focusing on animal models and clinical studies. Thorough research on the PubMed database was conducted to select relevant reviews elucidating EG structure and functions, as well as experimental studies addressing the problem. First, this review will center on the structure and functions of the EG. Subsequently, this review will delve into the role of BD in the degradation of the EG and explore the mechanisms involved in its alteration during the process of organ transplantation. Finally, therapeutic strategies aimed at preserving EG integrity and promoting graft’s function post-surgery are presented. In summary, this review concludes that several animal models have provided valuable insights into EG degradation during pathological conditions. These models have demonstrated the significant impact of EG degradation on graft functions and have also shown the effectiveness of certain treatments in enhancing the success of organ transplantation. However, knowledges and clinical studies in the field of EG alteration during organ transplantation are still limited. Further studies are required to expand understanding in this area and to broaden therapeutic options.

Date of Award	22 Jun 2023
Original language	English
Awarding Institution	University of Namur
Supervisor	Sophie Dogne (Supervisor)