SMAD2 and cardiac hypertrophy: These chemokines subsequently promote late cardiac infiltration of CCR2+ macrophages that express high levels of S00A8/A9, which activate ER stress/NF-κB/Nrlp3 signaling to skew macrophages toward the M1 phenotype and promote activation of the AKT/Calcineurin A and TGF-β/Smad2/3 pathways, leading to subsequent aggravation of cardiac hypertrophy and HF (Figure 9).