The novelty of our study includes: (i) the hemin-induced selective enhancement of the anti-inflammatory M2 phenotype in left-ventricular tissue of ZFs and parallel reduction of the proinflammatory macrophage M1 phenotype and MIP-1α, a chemokine implicated in macrophage infiltration; (ii) the hemin-dependent suppression of heart failure proteins such as osteopontin and osteoprotegerin; (iii) the suppression of inflammatory cytokines in ZFs; and (iv) the hemin-induced reduction of insulin resistance and improvement of cardiac function in ZFs. Here, SPP1 is linked to Insulin resistance.