Cardiac Allograft Vasculopathy : Molecular pathology of the transplanted heart

Abstract

Cardiac Allograft Vasculopathy (CAV) is a disease which has a high prevalence in Heart transplant (HTx) patients. It is characterized by concentric thickening of the wall of the coronary artery of the transplanted heart. The pathogenesis of CAV is complex; various cell types from both the host and the donor play a role. Activation of immunological components affects the vasculature of the allograft. Although in the past a lot of knowledge is gained about the processes that underlie the pathogenesis of CAV, there are still gaps in our knowledge. By clarifying the exact roles of all these different components, a solution for CAV may come in reach. We have the unique opportunity to study allograft vasculopathy in hearts after transplantation, collected at autopsy in our Pathology department.

The aim of this thesis was (1) to study the pathogenesis of Cardiac Allograft Vasculopathy on a morphological, cellular, and molecular level. Furthermore (2) the purpose of this thesis was to study the role of ectopic lymphoid structures surrounding CAV arteries. Understanding the role of these structures could provide therapeutic options. Ultimately, we aimed (3) to identify a molecular target and test the ability of this therapy in a well-established humanized mouse model for CAV.