Macrophage-specific Csf2ra deficiency significantly improved left ventricular systolic function post-MI and enhanced collagen scar maturation in a mouse model.
Does macrophage-specific Csf2ra deficiency improve left ventricular systolic function and remodeling following myocardial infarction in mice?
Macrophage-intrinsic CSF2RA signaling regulates inflammatory resolution and scar maturation after MI, suggesting CSF2RA inhibition as a potential therapeutic strategy to limit adverse cardiac remodeling.
Myocardial infarction (MI) triggers a robust inflammatory response that is essential for tissue repair but, when excessive or prolonged, drives pathological cardiac remodelling and heart failure. Colony-stimulating factor 2 (CSF2) signalling has been implicated in driving pro-inflammatory macrophage activation post-MI. Here, we investigated the role of macrophage-specific CSF2 receptor alpha (CSF2RA) signalling in post-MI remodelling using a tamoxifen-inducible genetic mouse model and permanent coronary artery ligation. Macrophage-specific Csf2ra deficiency significantly improved left ventricular systolic function post-MI without altering cardiac fibrosis burden. Functional improvement was associated with enhanced collagen scar maturation, characterised by an increased proportion of mature collagen fibres, and with accumulation of anti-inflammatory, pro-reparative macrophages within the infarct. These macrophage changes were accompanied by increased fibroblast density, consistent with altered macrophage–fibroblast crosstalk. Collectively, these findings identify macrophage-intrinsic CSF2RA signalling as a critical regulator of inflammatory resolution and scar maturation after MI and provide mechanistic support for the rationale of selective CSF2RA inhibition as a therapeutic strategy to limit adverse cardiac remodelling and improve post-infarction recovery.
Kremastiotis et al. (Fri,) conducted a other in Myocardial infarction. Macrophage-specific Csf2ra deficiency was evaluated on Left ventricular systolic function and cardiac fibrosis burden. Macrophage-specific Csf2ra deficiency significantly improved left ventricular systolic function post-MI and enhanced collagen scar maturation in a mouse model.