Breakthroughs in the Pathological Mechanism and Comprehensive Management of Pulmonary Hypertension

Pulmonary hypertension (PH) is a rare and life-threatening vascular disorder characterized by complex and multifactorial pathogenesis. Emerging evidence indicates that pulmonary vascular remodeling is driven by coordinated abnormalities in genetic susceptibility, epigenetic regulation, metabolic reprogramming, immune-inflammatory crosstalk, and DNA damage repair. Recent advances in multi-omics profiling, single-cell technologies, and high-resolution imaging have substantially improved the understanding of PH pathobiology and disease heterogeneity. Current therapeutic strategies mainly target the three classical vasoactive pathways to alleviate vasoconstriction and improve hemodynamics. Notably, (bone morphogenetic protein) BMP/transforming growth factor‑β1 (TGF-β) pathway-targeted therapy, represented by sotatercept, has initiated a new era of disease-modifying treatment aimed at reversing pulmonary vascular remodeling. In addition, emerging therapies targeting immune, hormonal, and metabolic pathways have demonstrated promising therapeutic potential. Despite significant progress in both basic and clinical research, major challenges remain, including precise phenotypic stratification, long-term therapeutic safety, and individualized treatment optimization. This review summarizes recent advances in the molecular mechanisms and comprehensive management of PH and highlights future directions for translational research and precision medicine.