Macrophage ITGAV is dispensable for post-infarction remodeling in mice and does not mediate fibronectin responses

Macrophages sense changes in their matrix environment through the integrins. In vitro, αV integrin (ITGAV) has been suggested to modulate a broad range of macrophage responses. However, the in vivo role of macrophage ITGAV in injury and repair remains unknown. Here we use myeloid cell and macrophage-specific ITGAV knockout mice and in vitro experiments to investigate the role of ITGAV signaling in repair and remodeling after myocardial infarction. ScRNA-sequencing and immunofluorescence show that ITGAV mRNA and protein are highly expressed in infarct macrophage subpopulations. Myeloid cell-specific and macrophage-specific loss of ITGAV have no significant effects on post-infarction remodeling and dysfunction and do not significantly affect macrophage recruitment, myofibroblast infiltration, collagen deposition and angiogenesis in the infarcted heart. In vitro, RNA-sequencing shows that the ITGAV activator fibronectin, which is abundantly expressed in healing infarcts, has profound effects on the macrophage transcriptome, inducing inflammatory, cell cycle and extracellular matrix proteolysis genes. These effects are independent of ITGAV. In conclusion, macrophage ITGAV does not play an important role in regulating repair, remodeling and fibrosis in a mouse model of myocardial infarction. The lack of functional impact may be attributed to the limited role of ITGAV in transducing fibronectin-mediated signals in macrophages.