Abstract P1020: Differential Contribution of Bone Marrow Cells to the Heart in Steady-state and after Repetitive Ischemia

Multiple studies have implicated the important role of migration of bone marrow (BM)-derived cells in heart after ischemia. Various BM-derived cells have been demonstrated to exert beneficial or detrimental effects in ischemia. But the response of BM to repetitive ischemia (RI) and the difference in contribution of this heterogenous population to the heart after RI remain elusive. Here, we applied an occluder on the left anterior descending coronary arteries of rats and they went under RI over a period of 10-17 days. This RI model induced coronary collateral growth and increased myocardial blood flow in the ischemic region after 10-17 days. We performed single- cell RNA sequencing and analysis of 24103 bone marrow transcriptomes isolated from the heart and bone marrow of rats in steady-state and after RI. Unsupervised clustering of cardiac neutrophils revealed 28 major clusters and 16 different cell types. Compared to steady state heart, proportion of BM derived macrophage mainly CD163 positive population was increased in the heart after RI. The proportion of BM derived natural killer cells was decreased markedly in the RI group. There was a slightly higher percentage of BM derived endothelial cells and lower smooth muscle cell and fibroblast in the RI group. While neutrophil degranulation, leukocyte activation, leukocyte migration are the major biological pathways in both groups, RI group showed activation of regeneration. We report heterogeneity of BM cells migrated to the heart during RI and redefine the BM that respond to heart ischemia and participate in induction of angiogenesis after RI.