Complement, Coagulation, and Fibrinolysis: The Role of the Endothelium and Its Glycocalyx Layer in Xenotransplantation

Transpl Int. 2024 Oct 15:37:13473. doi: 10.3389/ti.2024.13473. eCollection 2024.

Abstract

In xenotransplantation, the vascular endothelium serves as the first point of contact between the recipient's blood and the transplanted donor organ. The loss of the endothelium's ability to control the plasma cascades plays a critical role in the dysregulation of the complement and coagulation systems, which greatly contribute to graft rejection and hinder long-term xenograft survival. Although it is known that an intact glycocalyx is a key feature of a resting endothelium that exhibits optimal anticoagulant and anti-inflammatory properties, the role of the endothelial glycocalyx in xenotransplantation is barely investigated so far. Here, we discuss the central role of endothelial cells and the sugar-rich endothelial glycocalyx in regulating the plasma cascades, and how the loss of these functions contributes to graft damage and rejection. We highlight the importance of preserving the regulatory functions of both endothelial cells and the glycocalyx as strategies to improve xenotransplantation outcomes.

Keywords: complement and coagulation; endothelial glycocalyx; endothelium; plasma cascades; xenotransplantation.

Publication types

  • Review

MeSH terms

  • Animals
  • Blood Coagulation* / physiology
  • Complement System Proteins / metabolism
  • Complement System Proteins / physiology
  • Endothelial Cells / metabolism
  • Endothelium, Vascular / metabolism
  • Fibrinolysis* / physiology
  • Glycocalyx* / metabolism
  • Glycocalyx* / physiology
  • Graft Rejection*
  • Graft Survival
  • Heterografts
  • Humans
  • Transplantation, Heterologous*

Substances

  • Complement System Proteins

Grants and funding

The author(s) declare that financial support was received for the research, authorship, and/or publication of this article. This work was funded by the Swiss National Science Foundation grant (SINERGIA Xeno2Cure, grant agreement No. CRSII5198577).