The Role of Immunoresolvents in Atherosclerosis: A Mini-Review on Their Biology and Therapeutic Opportunities

Abstract

BACKGROUND AND AIMS: Atherosclerosis is a lipid-induced chronic inflammatory cardiovascular disorder denoted by the infiltration of immune cells and the agglomeration of lipids in the intima, the innermost layer, of the arteries of large and medium sizes. Defective efferocytosis is a sign of insufficient inflammation resolution that results in the agglomeration of secondarily necrotic macrophages and foam cells, and constitutes an advanced lesion having a necrotic lipid core, indicating plaque vulnerability. The inflammation resolution is an active, highly coordinated process governed by specialized pro-resolving lipid mediators (SPMs) or immunoresolvents, a group of bioactive lipid mediators that encompass arachidonic acid-derived lipoxins, omega-3 fatty acid eicosapentaenoic acid-derived E-series resolvins, docosahexaenoic acid-derived D-series resolvins, protectins, and maresins. These endogenously produced lipid mediators are resolution ligands functioning on distinct G-protein coupled receptors, thereby exhibiting the anti-inflammatory and pro-resolving effects, restoring tissue homeostasis and healing. Given the involvement of lipids and their pro- and anti-inflammatory derivatives in the pathogenesis of inflammatory states such as atherosclerosis, in this mini-review, we have tried to give a glance at the role of immunoresolvents in illness pathophysiology and the potential for pro-resolving therapeutics in atherosclerosis. METHODS: This mini-review utilized published papers available in electronic databases, including PubMed, Science Direct, and Google Scholar, to recognize pertinent sources through the following search key terms: "Atherosclerosis," "SPM," "Immunoresolvent," "Lipoxin," "Resolvin," "Protectin," and "Maresin" until February 2026. RESULTS: Recent investigations have shown that imbalances between pro-inflammatory lipid mediators and immunoresolvents are intimately linked to failed resolution and several common human disorders, including atherosclerosis. Moreover, dysregulation of resolving inflammation in atherosclerosis and other inflammatory diseases has been delineated in recent decades. CONCLUSION: Taken together, immunoresolvents could be regarded as new and hopeful therapeutic agents to be studied and utilized for treating atherosclerosis.