SIRT3 and Pelger-Huet anomaly: The availability of deficient-SIRT3 mice faces the challenge of PHA model development, since it has been reported that mouse PAH models may not develop pulmonary hypertension, RV hypertrophy, and RV failure regardless pulmonary artery remodeling; besides, some of the models show spontaneous reverse of pulmonary hypertension once the inductor is not present [85, 86].