At the mechanistic level, betaine may exert a cardioprotective effect by inhibiting oxidative stress, inflammation, and fibrosis by regulating the AMPK/nuclear factor erythroid 2-related factor 2 (Nrf2)/TGF-β signaling pathway (24), and enhance pulmonary hypertension and ischemia-reperfusion injury in animal models (Figure 6A). This evidence concerns the gene NFE2L2 and pulmonary arterial hypertension.