This paper provides a direct mechanism for NF-κB activation in a cardiac ischemic setting. It shows that the cytokine IL-34, which is upregulated after IR, activates both the canonical (p65) and non-canonical (p52/RelB) NF-κB pathways in macrophages. This NF-κB activation is shown to be the direct upstream driver of the chemokine CCL2, which in turn mediates further macrophage recruitment and polarization, exacerbating cardiac remodeling. This provides a specific, citable pathway for how NF-κB drives macrophage-mediated inflammation in ischemic heart disease. Here, CCL2 is linked to coronary artery disorder.