The role of lipoxins in cardiometabolic physiology and disease

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Cardiometabolic pathophysiology is increasing in prevalence as a result of the escalating obesity pandemic. The search for novel therapeutics is ongoing and the strong interrelationship between diabetes and cardiovascular disease places emphasis on the need for drugs that target both pathologies, without interlinking side effects. Impaired inflammatory resolution may be the common denominator driving metabolic syndrome, diabetes, and cardiovascular disease. An interesting therapeutic approach would therefore be to promote the inflammatory resolution to subvert cardiometabolic disease. Inflammatory resolution is regulated by specialized proresolving lipid mediators: the ω3-polyunsaturated fatty acid-derived protectins, resolvins and maresins, and the ω6-polyunsaturated fatty acid-derived lipoxin (LX) A4 and LXB4. Here, we review novel evidence of how LXs may reduce pathological features associated with cardiometabolic disease. Recent evidence shows that LXs promote the resolution of obesity-induced adipose inflammation and systemic pathology. Furthermore, LXs attenuate cardinal processes associated with atherosclerotic plaque formation, for example, neutrophil recruitment, activation, and neutrophil extracellular traps formation, while promoting a proresolving MΦ phenotype and enhancing efferocytosis. Finally, LXs inhibit angiogenic pathways, including endothelial proliferation and activation, while reducing platelet-neutrophil aggregation. Collectively, LXs may have therapeutic potential in attenuating cardiometabolic pathophysiology.

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