Lipoxygenase Pathways in the Regulation of Vascular Inflammation and Its Resolution

Inflammation is associated with vascular diseases, including atherosclerosis. The inflammatory response in the blood vessel involves cellular interactions between endothelial cells and monocytes/macrophages, and inflammatory mediators. Lipoxygenase (LOX) enzymes play an important role in inflammatory responses through the formation of lipid mediators. The 5-LOX pathway, primarily active in leukocytes such as monocytes/macrophages, converts arachidonic acid (AA) to leukotrienes (LTs), which are pro-inflammatory mediators that contribute to various vascular pathologies. In contrast, LOX pathways also generate specialized pro-resolving lipid mediators (SPMs), highlighting a dual role in both the initiation and resolution of inflammation. SPMs, formed by 5-LOX, 12-LOX and 15-LOX enzymes, are polyunsaturated fatty acid (PUFA)-derived anti-inflammatory and inflammation-resolving mediators that have important functions in the resolution of inflammatory processes. Dysregulation of the balance between pro-inflammatory leukotrienes and SPMs contributes to chronic vascular inflammation and disease progression. These mediators have been implicated in the treatment of vascular diseases with therapeutic strategies including LT receptor antagonists, 5-LOX-activating protein (FLAP) inhibitors, and approaches aimed at enhancing SPM pathways showing potential. This review provides an overview of the regulation of vascular inflammation and resolution by LOX pathways, and presents recent evidence on the role of LOX-derived lipid mediators in vascular inflammation and its resolution.