Our results show that CARP has an important role in inhibiting cardiac hypertrophy induced by pressure overload and continuous isoproterenol infusion, and reveal an important regulatory role for transforming growth factor-β (TGF-β) signaling and the mitogen-activated protein kinase (MAPK) cascade, specifically the MEK/ERK1/2 (MAPK/ERK kinase/extracellular signal-regulated kinase) pathway, in mediating attenuation of cardiac hypertrophy and fibrosis by CARP. Here, MAPK3 is linked to cardiac hypertrophy.