Contribution of cardiac macrophages to fibrosis following myocardial infarction 3504

Abstract Description Myocardial infarction, triggered by the disruption in blood supply to the cardiac muscle, results in necrosis of cardiac cells. Despite therapeutic options to restore circulation, limiting fibrotic scar formation remains a challenge. Fibrosis stems from an imbalance between extracellular matrix (ECM) production and degradation, disrupting tissue architecture. Macrophages, versatile immune cells, play a crucial role in this process. Macrophages exhibit high heterogeneity in phenotype, gene expression profile, and functions, potentially playing opposing roles in fibrosis by either stimulating ECM synthesis from fibroblasts or promoting its degradation. Understanding macrophage heterogeneity during tissue repair, especially their contribution to fibrosis, is crucial. This study explores macrophage contribution to post-infarction fibrosis. By identifying the cellular origin and anatomical location of macrophages in the ischemic heart, we revealed that a subset of monocytes recruited post-infarction differentiated into macrophages that persist in the fibrotic scar. Moreover, these macrophages are critical in limiting fibrotic scar size and preserving cardiac function post-infarction. These findings pave the way for a better understanding of the physio pathological processes leading to fibrotic scar formation and open new therapeutic opportunities to enhance the management of patients after myocardial infarction. Funding Sources Supported by the LabEx REVIVE (Stem cells in regenerative biology and medicine), FRM (French foundation for medical research) and ANR AgingImmunity (French National Research Agency) Topic Categories Cellular Adhesion, Migration, and Inflammation (CAM)