Specialized Pro‐Resolving Mediators as Emerging Players in Cardioprotection: From Inflammation Resolution to Therapeutic Potential

Aim: Timely myocardial reperfusion is essential for restoring blood flow to post-ischemic tissue, thereby reducing cardiac injury and limiting infarct size. However, this process can paradoxically result in additional, irreversible myocardial damage, known as myocardial ischemia–reperfusion injury (MIRI). The goal of this review is to explore the role of specialized pro-resolving mediators (SPMs) in atherosclerosis and MIRI, and to assess the therapeutic potential of targeting inflammation resolution in these cardiovascular conditions. Methods: This review summarizes current preclinical and clinical evidence on the involvement of SPMs in the pathogenesis of atherosclerosis and MIRI, acknowledging that several cellular and molecular aspects of their mechanisms of action remain to be fully elucidated. Results: MIRI is a complex phenomenon in which inflammation, initially triggered during ischemia and further amplified upon reperfusion, plays a central role in its pathogenesis. Various cellular and molecular players mediate the initial pro-inflammatory response and the subsequent anti-inflammatory reparative phase following acute myocardial infarction (AMI), contributing both to ischemia- and reperfusion-induced damage as well as to the healing process. SPMs have emerged as key endogenous immunoresolvents with potent anti-inflammatory, antioxidant, and pro-resolving properties that contribute to limit excessive acute inflammation and promote tissue repair. While dysregulated SPM-related signaling has been linked to various cardiovascular diseases (CVD), their precise role in AMI and MIRI remains incompletely understood. Conclusion: Targeting inflammation resolution may represent a promising therapeutic strategy for mitigating atheroprogression and addressing a complex condition such as MIRI.