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 (< 4 days post-event) when
compared to the subsequent remodeling phases.
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.
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© 2021 Published by Elsevier Inc.