Immunological and Fibrotic Mechanisms in Cardiac Allograft Vasculopathy

Abstract

Cardiac allograft vasculopathy (CAV) has a high prevalence among patients that have undergone heart transplantation. Cardiac allograft vasculopathy is a multifactorial process in which the immune system is the driving force. In this review, the data on the immunological and fibrotic processes that are involved in the development of CAV are summarized. Areas where a lack of knowledge exists and possible additional research can be completed are pinpointed. During the pathogenesis of CAV, cells from the innate and the adaptive immune system cooperate to reject the foreign heart. This inflammatory response results in dysfunction of the endothelium and migration and proliferation of smooth muscle cells (SMCs). Apoptosis and factors secreted by both the endothelium as well as the SMCs lead to fibrosis. The migration of SMCs together with fibrosis provoke concentric intimal thickening of the coronary arteries, which is the main characteristic of CAV.

Peak oxygen uptake and self‐reported physical health are strong predictors of long‐term survival after heart transplantation

“…The mechanisms of development are described as both immunological and non-immunological, possibly modifiable factors (54). It can be detected by coronary angiography, but intravascular ultrasound (IVUS) is now more frequently used, and is a superior diagnostic tool to detect early changes in intimal thickening (early CAV) (55).…”

Testing the Efficacy of Contrast-Enhanced Ultrasound in Detecting Transplant Rejection Using a Murine Model of Heart Transplantation

“…Early endothelial injuries have been the precursors to overt atherosclerotic lesions as well as cardiac allograft vasculopathy (38). Classical pathological manifestations of graft rejection rely heavily on the presence of adaptive immune cells (such as T cell infiltrates) that are late players of graft rejection (39). The biological markers representative of early innate immune activation are lacking in traditional pathological examination.…”

Coronary artery intimal thickening and ventricular dynamics in pediatric heart transplant recipients

“…Improvements in immunosuppressive agents have played an important role in improving the health and longevity after heart transplantation; however, they have been implicated as a contributor to the development of cardiac allograft vasculopathy (CAV) . Characterized by an accelerated, progressive coronary artery intimal thickening, CAV is independent of acute allograft rejection, and is considered a form of chronic rejection . One in 4 pediatric heart transplant deaths are attributed to CAV, which affects approximately 50% of children by 15 years post‐transplant .…”