MAPK3 and heart failure: While AT1 receptor sensitization is largely mediated by the RKIP-GRK2 interaction, the development of cardiotoxic lipid load is attributed to Raf-Erk1/2 pathway inhibition, which leads to heart failure-promoting and adipogenic Pparg activation by inhibition of Pparg phosphorylation on serine-273 (8, 33).