Yinhui Sun, Rongzhen Ding, Xianli Su, Li Qin, Lihuai Wang, Jian Yi, Ruicheng Hu, Shuying You, Zhenfei Tan, Aiguo Dai
Pulmonary hypertension (PH) is a multifaceted disorder characterized by the crucial involvement of activated hypoxia-inducible factors (HIFs). Recent investigations have unveiled HIFs' ability to orchestrate a wide array of signaling cascades, encompassing voltage-gated potassium channels, non-selective cation channels (NSCCs), Ca2+/PKC/MAPKs, PI3K/Akt, RhoA/ROCK, Notch, VEGF, and miRNA pathways. The interplay of these signaling cascades drives critical events, namely hypoxic pulmonary vasoconstriction (HPV) and hypoxic pulmonary vascular remodeling (HPVR), which collectively contribute to the pathogenesis of PH. This review summarizes the role of HIF signaling in hypoxic pulmonary vasoconstriction, pulmonary vascular remodeling, metabolic reprogramming, inflammation, non-coding RNA regulation, and emerging HIF-targeted therapies.