Myeloid-derived modulators shape the pathophysiological roles of TGF-β in post-infarct myocardial remodeling

Transforming growth factor-β (TGF-β) plays diverse roles in post-infarct myocardial remodeling, ranging from inflammatory injury to tissue repair. Although these apparently opposing functions have traditionally been attributed to the timing of TGF-β signaling, increasing evidence suggests that local regulatory mechanisms within the infarct microenvironment critically shape its pathophysiological effects. In this review, we propose that myeloid-derived modulators define the context-dependent pathophysiological roles of TGF-β after myocardial infarction. We focus on two mechanistically distinct regulators: glycoprotein A repetitions predominant (GARP), a membrane-bound activator of latent TGF-β that promotes localized inflammatory signaling, and leucine-rich α2-glycoprotein-1 (LRG1), a secreted modulator that promotes angiogenesis and tissue repair. We discuss the emerging importance of these mechanistically distinct regulators in shaping local TGF-β signaling niches that orchestrate the transition from inflammatory injury to reparative remodeling and highlight their potential as therapeutic targets for precision modulation of post-infarct remodeling.