Cardiac allograft vasculopathy and the endothelial glycocalyx: a missing link?

Cardiac allograft vasculopathy (CAV) is a significant contributor to graft loss following heart transplantation, with a linear cumulative incidence over time. Both immune and non-immune risk factors are associated with the development of CAV, however, a cohesive mechanistic link between them is yet to be established. Immune and non-immune risk factors may be linked to CAV via disturbance of the endothelial glycocalyx (EGX), a protective vascular structure whose functions appear to be impaired in the context of CAV progression. In this review, we present this hypothesis, summarizing the evidence and implications for EGX loss during CAV. We synthesize a novel model that places EGX disturbance at the center of CAV pathogenesis. As a currently incurable disease, we highlight that this new model may unlock new approaches to prevention and therapy and requires further research.