RT Journal Article SR Electronic T1 M2 Macrophage Exosomes Reverse Cardiac Functional Decline in Mice with Diet-Induced Myocardial Infarction by Suppressing Type 1 Interferon Signaling in Myeloid Cells JF bioRxiv FD Cold Spring Harbor Laboratory SP 2024.09.13.612924 DO 10.1101/2024.09.13.612924 A1 Ng, Martin A1 Gao, Alex S. A1 Phu, Tuan Anh A1 Vu, Ngan K. A1 Raffai, Robert L. YR 2024 UL http://biorxiv.org/content/early/2024/09/19/2024.09.13.612924.abstract AB Effective treatment strategies to alleviate heart failure that develops as a consequence of myocardial infarction (MI) remain an unmet need in cardiovascular medicine. In this study, we uncovered that exosomes produced by human THP-1 macrophages cultured with the cytokine IL-4 (THP1-IL4-exo), reverse cardiac functional decline in mice that develop MI as a consequence of diet-induced occlusive coronary atherosclerosis. Therapeutic benefits of THP1-IL4-exo stem from their ability to reprogram circulating Ly-6Chi monocytes into an M2-like phenotype and suppress Type 1 Interferon signaling in myeloid cells within the bone marrow, the circulation, and cardiac tissue. Collectively, these benefits suppress myelopoiesis, myeloid cell recruitment to cardiac tissue, and preserve populations of resident cardiac macrophages that together mitigate cardiac inflammation, adverse ventricular remodeling, and heart failure. Our findings introduce THP1-IL4-exo, one form of M2-macrophage exosomes, as novel therapeutics to preserve cardiac function subsequent to MI.Competing Interest StatementThe authors have declared no competing interest.