Omega-6 polyunsaturated fatty acids and their metabolites: a potential targeted therapy for pulmonary hypertension

Pulmonary hypertension (PH) is a progressive and life-threatening cardiopulmonary disease that is not uncommon. The modulation of the pulmonary artery (PA) involves various fatty acids, including omega-6 polyunsaturated fatty acids (ω-6 PUFAs) and ω-6 PUFAs-derived oxylipins. These lipid mediators are produced through cyclooxygenase (COX), lipoxygenase (LOX), cytochrome P450 (CYP450), and non-enzymatic pathways. They play a crucial role in the occurrence and development of PH by regulating the function and phenotype of pulmonary artery endothelial cells (PAECs), pulmonary artery smooth muscle cells (PASMCs), pulmonary fibroblasts, alveolar macrophages, and inflammatory cells. The alterations in ω-6 PUFAs and oxylipins are pivotal in causing vasoconstriction, pulmonary remodeling, and ultimately leading to right heart failure in PH. Despite the limited understanding of the PH pathophysiology, there is potential for novel interventions through dietary and pharmacological approaches targeting ω-6 PUFAs and oxylipins. The aim of this review is to summarize the significant advances in clinical and basic research on omega-6 PUFAs and oxylipins in pulmonary vascular disease, particularly PH, and to propose a potential targeted therapeutic modality against omega-6 PUFAs.