Furthermore, cardiac ASK1 overexpression induced exacerbated cardiac hypertrophy, fibrosis, dysfunction, and apoptosis following long-term pressure overload that was associated with enhanced ASK1-mediated phosphorylation of MKK6 and JNK activation [98], suggesting a role for ASK1/MKK6/JNK signaling in cardiac maladaptation to pathologic stimuli. This evidence concerns the gene MAP2K6 and cardiac hypertrophy.