Targeting NR4A1 (Nur77) in Macrophage Polarization: Molecular Mechanisms and Translational Prospects for Cardiac Repair After Myocardial Infarction

Figures

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  Figure 1. Schematic representation of NR4A signaling pathways proposed from preclinical and mechanistic studies. Microenvironmental cues associated with myocardial injury can activate HIF-1α, cAMP/PKA, and p38 MAPK–NF-κB pathways, thereby inducing NR4A expression and influencing macrophage transcriptional programs. Arrows indicate the direction of signaling pathways and regulatory relationships. Colors are used only for visual distinction and do not represent specific biological categories. Created with BioGDP.com. Abbreviations: HIF-1α, hypoxia-inducible factor 1 alpha; cAMP, cyclic adenosine monophosphate; PKA, protein kinase A; MAPK, mitogen-activated protein kinase; NF-κB, nuclear factor kappa B; DAMPs, damage-associated molecular patterns; NR4A, nuclear receptor subfamily 4 group A.

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  Figure 2. Temporal dynamics of macrophage polarization and consequences for post-infarct remodeling. In experimental murine models of myocardial infarction, Ly-6Chigh monocyte-derived M1 macrophages initially clear necrotic tissue and degraded matrix, whereas subsequent reprogramming of resident M1 cells and recruitment of Ly-6Clow monocytes generate a reparative M2-like pool that supports collagen deposition, neovascularization, and ventricular stability; disruption of this transition results in persistent inflammation, adverse remodeling, and chronic heart failure. Arrows indicate the progression of macrophage responses, and the colors distinguish the inflammatory and reparative phases after MI. Created with BioGDP.com.