Figure 2.

Diagram of PAH pathological mechanism. Three classical pathways; ET-1 binds to ETA and ETB receptors to promote intracellular Ca²⁺ release and Ca²⁺ channel opening, leading to increased intracellular Ca²⁺ and vascular remodeling; prostacyclin binds to GPCR and IP receptors, activating adenylate cyclase, converting ATP to cAMP and inhibiting cell proliferation by activating PKA and Epac; NO binds to GC, converting GTP to cGMP, thereby activating downstream PKG and causing vascular diastole. Immune cells and pulmonary hypertension, DCs stimulate T cell activation, T cells participate in pulmonary vascular remodeling by producing IL, TNF-α, IFN-γ, B cells participate in pulmonary vascular remodeling by over-secreting antibodies, cytokines, etc. Mast cells participate in the development of PAH by producing large amounts of IL-6, while reducing IL-6 production or inhibiting mast cell activation can reduce B lymphocyte production and can alleviate PAH. EC damages will release microvesicles, which contain miRs, and others, these MVs will stimulate macrophages to secrete cytokine such as TGF-β, and then stimulate PASMC proliferation.