Single Cell and Spatial Transcriptomics Identify Novel Immune-Stromal Interactions in Cardiac Allograft Vasculopathy

Cardiac allograft vasculopathy (CAV) is the leading cause of mortality in heart transplant recipients. Despite the prevalence of CAV, there are no targeted therapeutic options to prevent or reverse disease progression, and patients ultimately require retransplant. CAV is defined by progressive neointimal hyperplasia in donor heart coronary arteries, leading to luminal obliteration and ultimately allograft failure or sudden cardiac death. Although immune and stromal cell interactions are believed to play a key role in CAV pathogenesis, the specific cellular players and molecular signals driving disease remain undefined. In this study, we leverage single-cell RNA sequencing and spatial transcriptomics of human coronary arteries to transcriptionally characterize CAV and define the neointimal microenvironment. We compare arteries with CAV to atherosclerotic coronary artery disease and non-disease controls to identify a unique CAV transcriptional signature.