Satoh et al. [75] showed that long-term treatment with17β-Estradiol (E2) improved congestive heart failure (CHF) in rats by antioxidative mechanism that involved thioredoxin (Trx) upregulation, the inhibition of Rac1(small GTPase-) mediated NADPH oxidase activity, and the apoptosis signal-regulating kinase 1(ASK-1)/JNK/p38-mediated apoptosis. The gene discussed is MAPK8; the disease is congestive heart failure.