Gundewar et al. [73] have carried out some experiments that metformin could significantly improve left ventricular (LV) function and survival by AMPK and its downstream mediators activation, peroxisome proliferator-activated receptor γ coactivator 1-α (PGC-1α) and eNOS in a murine model of HF. The gene discussed is NOS3; the disease is hydrops fetalis.