MAPK8 and hypertensive heart disease: The underlying pathways and cellular mediators that are activated to mediate the pathology of heart failure in hypertensive heart disease include peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) and PGC-1β (64), GPCRs, p38, ERK1/2, JNK, CAMKII, protein kinases (type C, G, and A), Growth factor-mediated stimulation of mechanistic target of rapamycin (mTOR) (74), epigenetic modulators (such as NFAT, MEF2) and transient receptor potentials (74, 76).