Pulmonary Hypertension Molecular Switch: HIF Signaling Pathway

Neonates and infants with FOXF1 mutation develop alveolar capillary dysplasia with misalignment of pulmonary veins (ACD/MPV), which is typically considered a uniformly fatal neonatal lung disorder due to marked hypoxemic respiratory failure with severe pulmonary hypertension (PH).

Mechanosensitive cation channels expressed in pulmonary arterial smooth muscle (SMC) and endothelial (EC) cells contribute to the regulation of vasoconstriction and vasodilation of the pulmonary vasculature.

Pulmonary arterial hypertension (PAH) is a progressive vasculopathy leading to right-sided heart failure. We have shown previously that the (NOD-like-receptor-3) NLRP3 inflammasome is activated in end-stage disease of the monocrotaline and aortocaval shunt (MCT/ACS) neointimal PAH rat model. 

Originally named T-cell-originated Lymphokine-activated killer protein kinase (TOPK), PDZ-Binding Kinase (PBK) is a serine/threonine kinase that is a member of the family of mitogen-activated protein kinases (MAPKKs), which is overexpressed in lung cancer and interstitial pulmonary fibrosis (IPF).