Additionally, low level of PTEN and phosphorylated-PTEN was attributed to ubiquitination-mediated degradation in monocrotaline-induced PAH rat, and decreased PTEN expression led to an increase in phosphorylated Akt, inactivation of cell-cycle regulatory proteins p53,p21, and p27, and accumulation of cyclin-D1 [122]. Here, AKT1 is linked to pulmonary arterial hypertension.