Targeting PDGFR, EGFR, FGFR, and VEGFR: Key Receptor Tyrosine Kinases‐Driven Metabolic Reprogramming in Pulmonary Arterial Hypertension

Pulmonary arterial hypertension (PAH) is a rare and life-threatening pulmonary vascular disease distinguished by vasoconstriction and remodeling of the pulmonary artery, leading to sustained elevated pulmonary artery pressure, right ventricular failure, and even death. Receptor tyrosine kinases (RTKs) are critical in PAH pathogenesis, and targeted therapies against RTKs are becoming a research hotspot due to their potential to inhibit cell proliferation and right ventricular hypertrophy. Abnormal activation of RTKs induces downstream signaling cascades, including metabolic reprogramming through multiple regulatory crosstalk, to meet high energy requirements during cell proliferation. However, the crucial connection between metabolic reprogramming and RTKs in PAH remains largely unexplored. In this review, we focus on four key RTKs: Platelet-Derived Growth Factor Receptor (PDGFR), Epidermal Growth Factor Receptor (EGFR), Fibroblast Growth Factor Receptor (FGFR), and Vascular Endothelial Growth Factor Receptor (VEGFR) in the metabolic reprogramming of PAH and explore hypotheses that require further validation. The aim is to highlight how these mechanisms can be applied to develop better therapeutic strategies.