Likewise, ANG II activated its downstream kinase JNK, increased IGF-IIR expression through AT1R; JNK activation has been shown to degrade sirtuin 1 (SIRT1) via the proteasome and result in heat shock transcription factor 1 acetylation induced IGF-IIR expression for developing cardiac hypertrophy and apoptosis [64]. Here, MAPK8 is linked to cardiac hypertrophy.