The CCL2 network in pulmonary hypertension: Potential therapeutic targets

Pulmonary hypertension (PH) is a progressive and life-threatening disease characterized by pulmonary vascular remodeling, inflammation, and right ventricular dysfunction. Increasing evidence suggests that the chemokine CCL2 and its receptor CCR2 are critically involved in PH pathogenesis by promoting inflammatory cell recruitment, macrophage activation, and vascular remodeling. In this review, we summarize the emerging roles of the CCL2/CCR2 axis across different PH subtypes, including pulmonary arterial hypertension, PH associated with left heart disease, PH associated with chronic lung disease, and chronic thromboembolic PH. We also discuss the current pharmacological strategies targeting this pathway, including neutralizing antibodies, small-molecule CCR2 antagonists, and combination approaches. Finally, we highlight key challenges that remain to be addressed, including pathway redundancy, cell type specificity, and the need for robust biomarkers to identify patients most likely to benefit from CCL2/CCR2-targeted therapy.