Eicosapentaenoic acid improves outcome in acute myocardial infarction

• Applicant: Privatdozent Dr. Amin Polzin
• Subject Area: Cardiology, Angiology ; Analytical Chemistry ; Biochemistry ; Medical Informatics and Medical Bioinformatics
• Term: since 2023
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 510844896

Theoretical framework: Cardiovascular disease (CVD) is the leading cause of death in the western world. Besides mortality, acute myocardial infarction and consecutive heart failure are associated with substantial morbidity. Therefore, socioeconomic importance is enormous. Outcome after AMI is determined by myocardial healing after interventional reperfusion. Platelets are crucial in the genesis of thrombosis and subsequent vessel occlusion in AMI. Additionally, they are involved in the orchestration of post-ischemic myocardial inflammation. Hyperlipoproteinemia is a strong risk factor for the development of CVD. On the other hand, the role of unsaturated fatty acids (PUFA) is still controversial. The REDUCE-IT trial showed that the omega-3 PUFA icosapent ethyl (IPE), which is the ethyl ester of the bioactive metabolite eicosapentaenoic acid (EPA), significantly reduced cardiac risk in statin-treated patients with highly elevated triglycerides. On the contrary, high PUFA membrane content leads to rapid lipidomic remodeling in cell membranes and upregulation of saturated lipids and cholesterol. This could have adverse effects on the cardiovascular system. The PUFA membrane content is highly dependent on nutrition, genetic factors, and co-morbidities. In preliminary work, we discovered a novel mechanism of PUFA supplementation, directly and competitively interacting with arachidonic acid at the active site of platelet COX- 1. This subsequently reduces platelet reactivity and arterial thrombosis. Hypothesis: Now we hypothesize that enhanced platelet membrane EPA content improves outcome after AMI via interaction of EPA with AA at the level of platelet COX1 leading to reduced inflammation and improved myocardial healing. Furthermore, in a translational pilot study in STEMI patients, we will identify that EPA membrane PUFA content and their derived mediators are associated with myocardial healing after STEMI. Methodical approach: In-vivo and ex-vivo rodent models will be applied to investigate the effect of PUFA supplementation on cardioprotection. Additionally, a translational pilot trial will be conducted in patients with STEMI. Multiomics next-generation approaches will be applied to dissect platelets membranes and signaling lipidomes in murine and human samples. Level of originality: The application of next-generation omics tools for personal risk management, based on the identification and prediction of individual lipid biomarkers in platelet-biology during AMI and nutritional treatment, is a unique approach. Above all, the acquired datasets and computational models will pave the road for nutritional intervention after AMI. Primary researchers involved: The translational and interdisciplinary project involves Prof. Robert Ahrends (Department of Analytical Chemistry, University of Vienna, Austria) as supervising PI as well as PD Dr. Amin Polzin (Heinrich Heine University Hospital Düsseldorf Division of Cardiology, Germany).

• DFG Programme: Research Grants
• International Connection: Austria
• Cooperation Partner: Professor Dr. Robert Ahrends, Ph.D.