Arachidonic acid synergizes with aspirin preventing myocardial ischaemia–reperfusion injury and mitigates bleeding risk

作者：Shaletanati Talabieke, Xuejian Yang, Jianfeng Yang, Qing Wan, Dekun Zhu, Haojie Rao, Yifei Wu, Zengrong Chen, Huihui Li, Pengfei Xu, Hong Chen, De‐Pei Liu, Xu Zhang, Garret A. FitzGerald, Miao Wang · 发表于：Cardiovascular Research · 年份：2025 · DOI：10.1093/cvr/cvae254 · 被引用次数：13 · 研究领域：Inflammatory mediators and NSAID effects、Cardiac Ischemia and Reperfusion、Eicosanoids and Hypertension Pharmacology

AIMS: The therapeutic efficacy of coronary revascularization is compromised by myocardial ischaemia-reperfusion (MI/R) injury. Higher levels of circulating arachidonic acid (AA) are reportedly associated with lower risk of cardiovascular disease. The cyclooxygenase (COX) pathway metabolizes AA into prostaglandins (PGs) and the platelet-activating thromboxane A2 (TXA2), which is inhibited by aspirin. We aimed to explore whether AA or its combination with aspirin modulates MI/R injury and aspirin-caused gastric bleeding. METHODS AND RESULTS: Mice were subjected to 30-min coronary artery ligation followed by reperfusion. AA reduced MI/R injury in mice, and its combination with aspirin provided further cardioprotection. Aspirin inhibited MI/R-triggered platelet activation and ameliorated microvascular obstruction immediately upon reperfusion, whereas AA improved microvascular perfusion at a later stage of reperfusion, coinciding with increased coronary vasodilatation. Co-administration of AA and aspirin markedly reduced cardiac neutrophil infiltration and vascular permeability and improved microcirculation. AA increased urinary metabolites of PGI2 and PGE2, not TXA2, and this selective augmentation was further enhanced by co-treatment with aspirin. Elevation in PGI2 and PGE2 correlated with reduced infarction and improved ventricular function, and inhibiting COX-2 attenuated the synergistic cardioprotection. Furthermore, oral administration of AA with aspirin after reperfusion pr...