Our study indicates that dacomitinib inhibited hypoxia-induced cell cycle progression, proliferation, migration, and autophagy of PASMCs, thereby attenuating pulmonary vascular remodeling and development of PAH via the PI3K-AKT-mTOR signaling pathway.
Therefore, combinatory treatment with DCA and PI3K inhibitors may represent a novel therapeutic strategy for the reversal of apoptosis resistance exhibited by PASMCs as a result of mitochondrial bioenergetic abnormalities, as well as the treatment of pulmonary vascular remodelling in pulmonary arterial hypertension.
In addition, LY294002, a PI3K inhibitor, reduced the PI3K and p‑Akt protein expression in the PAECs and reversed the effects of miR‑371b‑5p overexpression on the apoptosis of PAECs in rats with monocrotaline‑induced PAH.
Inhibition of proteasome function ameliorates pulmonary arterial remodeling by suppressing UPS-mediated PTEN degradation and subsequent inhibition of PI3K/Akt pathway, indicating that UPS might be a novel target for prevention of PAH.
Sprague-Dawley male rats were randomly divided into 4 groups: control group (n=8), PAH group (n=8), genistein treament group with three different doses (n=8 in each dose group) and group of PI3K inhibitor LY294002.
These findings suggested that the mitogen‑activated protein kinase and PI3K/Akt signaling pathways, and HIF‑1 may perform a specific function in the pathogenesis of PAH.