NPPA and heart failure: Therefore, the synergistic potentiation of the HO-adiponectin-ANP axis and insulin signaling with corresponding ablation of extracellular matrix/heart failure proteins, the reduction of oxidative stress, and inflammation mediators such as macrophage M1 phenotype, MIP-1α and MCP-1, TNF-α, IL-6, IL-1β, ET-1, and 8-isoprostane are among the multifaceted mechanisms by which hemin therapy improved cardiac function.