CHARACTERIZING THE IMMUNE PROFILE OF HUMAN PERICARDIAL FLUID

BACKGROUND The human pericardial space is an enclosed cavity that provides a homeostatic environment for optimal physiologic functioning of the heart. The contents of this space include pericardial-fluid (PF). Pericardial-fluid can be an appealing target for future therapeutic interventions that can facilitate precision medicine. Our team recently discovered a population of immune cells, Gata6-expressing macrophages, to populate the pericardial space where they rapidly relocate to the heart and help mitigate post-infarct cardiac fibrosis. Human pericardial immune cells may contribute to similar clinical benefits, however to date no study has comprehensively evaluated the immune cell composition of human PF following acute coronary events. Herein, we characterize the PF immune cell profile of patients undergoing cardiac surgery. METHODS AND RESULTS PF was collected from patients (n = 32) undergoing elective coronary artery bypass graft (CABG) surgery (ACS group, n = 23) and valve replacement/repair surgery (non-ACS group, n=9). Patients undergoing CABG surgery were recruited based on days post-diagnosis of an acute coronary syndrome (ACS): Inflammatory phase, surgery was done less than 4 days from event (n = 4); Proliferative phase, surgery was done between 4 and 14 days from event (n = 13); and Maturation phase, surgery was done after 14 days from event (n = 6). Patients undergoing valvular surgery presented with aortic stenosis (n = 7) or mitral regurgitation (n = 2). The patient population (mean age 64) included 81% men. We found the PF cells to be composed of two macrophage populations, two classical dendritic cell populations, inflammatory dendritic cells, neutrophils, T-cells, B-cells, and two natural killer cell populations. CD163hi-macrophages and T-cells were the most represented populations accounting for over 60% of total immune cells. Gata6-expression evaluation revealed that the CD163hi-macrophage population represented the main Gata6-expressing myeloid cell population within the PF. Notably, compared to non-ACS controls, ACS patients had significantly fewer CD163hi-macrophages. Stratifying the ACS group based on timing following the coronary event further demonstrated this reduction in CD163hi-macrophages, which was more pronounced in the early inflammatory phase ( CONCLUSION As a homeostatic niche, the pericardial space can be a good representation of cardiac health. In this study, we comprehensively characterize the immune cell profile of human PF. In the era of precision and personalized medicine, a better understanding of PF immune cell function will help inform pericardial targeted strategies to enhance myocardial recovery post injury, or attenuate pro-remodeling inflammatory pathways.