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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.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods and results<\/jats:title>\n                  <jats:p>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 provided a maximal cardioprotection and abolished aspirin-caused gastric bleeding.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>AA synergizes with aspirin in protecting against MI\/R injury, while minimizing the related bleeding risk, a major concern for patients with acute myocardial infarction. This is attributable to the selective augmentation of PGI2 and PGE2 that is amplified by TXA2 suppression by aspirin, underscoring improved microcirculation and ameliorated inflammation.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/cvr\/cvae254","type":"journal-article","created":{"date-parts":[[2025,1,9]],"date-time":"2025-01-09T08:30:26Z","timestamp":1736411426000},"page":"775-787","source":"Crossref","is-referenced-by-count":14,"title":["Arachidonic acid synergizes with aspirin preventing myocardial ischaemia\u2013reperfusion injury and mitigates bleeding risk"],"prefix":"10.1093","volume":"121","author":[{"given":"Shaletanati","family":"Talabieke","sequence":"first","affiliation":[{"name":"State Key Laboratory of Cardiovascular Disease, Clinical Pharmacology Center, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences & Peking Union Medical College , 167 Beilishi Road, Xicheng District, Beijing 100037 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Peking Union Medical College , 167 Beilishi Road, Xicheng District, Beijing 100037 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yifei","family":"Wu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Cardiovascular Disease, Clinical Pharmacology Center, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences & Peking Union Medical College , 167 Beilishi Road, Xicheng District, Beijing 100037 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zengrong","family":"Chen","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Cardiovascular Disease, Clinical Pharmacology Center, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences & Peking Union Medical College , 167 Beilishi Road, Xicheng District, Beijing 100037 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Laboratory of Cardiovascular Disease, Clinical Pharmacology Center, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences & Peking Union Medical College , 167 Beilishi Road, Xicheng District, Beijing 100037 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"De-Pei","family":"Liu","sequence":"additional","affiliation":[{"name":"Key Laboratory of Common Mechanism Research for Major Diseases, Department of Biochemistry and Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences & Peking Union Medical College , Beijing 100005 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xu","family":"Zhang","sequence":"additional","affiliation":[{"name":"Tianjin Key Laboratory of Metabolic Diseases, The Province and Ministry Co-sponsored Collaborative Innovation Center for Medical Epigenetics, Center for Cardiovascular Diseases, Research Center of Basic 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