Targeted Circulating Lipid Mediators and Immune Cell Gene Transcripts After ST-Elevation Myocardial Infarction

Residual inflammation drives atherogenesis to atherosclerosis and myocardial infarction, which triggers acute inflammation. In preclinical studies, polyunsaturated fatty acids-derived specialized pro-resolving mediators (SPMs) have been shown to promote recovery after MI, in contrast to pro-inflammatory lipid mediators (PIMs). However, the dynamic changes of lipid mediators after ST-elevation myocardial infarction (STEMI), particularly after percutaneous coronary intervention (PCI) and respective gene transcripts, are poorly understood. Therefore, the study aimed to assess the early dynamic changes in circulating lipid mediators and lipid pathway transcripts in STEMI patients who undergo PCI. In this prospective observational clinical study, patients with STEMI (n=10) and control subjects (n=6) were included. Plasma samples for lipid mediator profiling (targeted oxylipids) and whole blood for inflammation-related transcript expression were collected at baseline before PCI, 2 hours, and 24 hours post-PCI. A total of 10 STEMI patients received PCI with a mean age of 53.3 years, 90% male. Linoleic acid and DPA levels were higher in STEMI patients. A subset of PIM levels (HETEs, PGE₂) were elevated at the baseline, with a subsequent decrease in circulating levels at 2 hours after PCI (TXB₂, LTB₄, 20-OH-LTB₄). A subset of SPM levels (HEPEs) were elevated at the baseline of STEMI suggestive overlap of inflammation-resolution signaling. The temporal kinetics of LMs showed that both the initiation of inflammation and the resolution process start simultaneously and continue as an endogenous repair mechanism during STEMI. Therefore, approaches to increase these endogenous bioactive resolution mediators content and/or efficacy before PCI should be considered in treating MI patients.