The prognostic and therapeutic significance of polyunsaturated fatty acid‐derived oxylipins in ST‐segment elevation myocardial infarction

• DOI: 10.1002/imt2.266
• Publication Date: 2025-01-10T06:34:20Z
• Authors: Zhiyong Du; Yingyuan Lu; Ying Ma; Yunxiao Yang; Wei Luo; Sheng Liu; Ming Zhang; Yong Wang; Lei Li; Chun Li; Wei Wang; Hai Gao
• Keywords: Elevation (ballistics)

Polyunsaturated fatty acid-derived oxylipins regulate systemic inflammation and exert cardiovascular effects, yet their role in ST-segment elevation myocardial infarction (STEMI) remains unclear. Herein, we used targeted metabolomics machine learning algorithms to develop an oxylipin-based risk model accurately predict recurrent major adverse events (MACE) after STEMI two independent prospective cohorts with 2 years of follow-up. The vivo effects significant oxylipin predictors were explored via a murine ischemia‒reperfusion functional metabolomics. Among the 130 plasma detected discovery cohort (n = 645), patients without MACE exhibited differences variety subclasses. We constructed prediction that showed powerful performance predicting (predictive accuracy: 91.5%). predictive value marker panel was confirmed external validation 89.9%; n 401). Furthermore, found anti-inflammatory/pro-resolving (ARO) predictor better prognostic than pro-inflammatory both cohorts. Compared treatment panel, combined six ARO predictors, including 14,15 epoxy-eicosatrienoic acid, 14(15)-epoxy-eicosatetraenoic 12,13-epoxy-octadecenoic lipoxin A4, resolving D1, 6 keto-prostaglandin F1 cardiac activities synergistic metabolic actions infarction‒reperfusion mice. also mechanistically identified important restraining ceramide/lysophosphatidylcholine synthesis inhibiting inflammatory responses. Overall, present study depicted landscape profiles largest worldwide. Our results highlight great potential bioactive therapeutics STEMI.