Infliximab Limits Injury in Myocardial Infarction

作者：Christopher Livia, Sara S. Inglis, Ruben Crespo‐Diaz, Skylar A. Rizzo, Ryan Mahlberg, Monique S Bagwell, Matthew L. Hillestad, Satsuki Yamada, Dhivya Vadhana Meenakshi Siddharthan, Raman Deep Singh, Xing Li, D. Kent Arrell, Paul G. Stalboerger, Tyra A. Witt, Abdallah El Sabbagh, Munveer Rihal, Charanjit S. Rihal, André Terzic, Jozef Bartúnek, Atta Behfar · 发表于：Journal of the American Heart Association · 年份：2024 · DOI：10.1161/jaha.123.032172 · 被引用次数：14 · 研究领域：Cardiac Fibrosis and Remodeling、Signaling Pathways in Disease、Acute Myocardial Infarction Research

Background The purpose of this study was to investigate a therapeutic approach targeting the inflammatory response and consequent remodeling from ischemic myocardial injury. Methods and Results Coronary thrombus aspirates were collected from patients at the time of ST‐segment–elevation myocardial infarction and subjected to array‐based proteome analysis. Clinically indistinguishable at myocardial infarction (MI), patients were stratified into vulnerable and resilient on the basis of 1‐year left ventricular ejection fraction and death. Network analysis from coronary aspirates revealed prioritization of tumor necrosis factor‐α signaling in patients with worse clinical outcomes. Infliximab, a tumor necrosis factor‐α inhibitor, was infused intravenously at reperfusion in a porcine MI model to assess whether infliximab‐mediated immune modulation impacts post‐MI injury. At 3 days after MI (n=7), infliximab infusion increased proregenerative M2 macrophages in the myocardial border zone as quantified by immunofluorescence (24.1%±23.3% in infliximab versus 9.29%±8.7% in sham; P <0.01). Concomitantly, immunoassays of coronary sinus samples quantified lower troponin I levels (41.72±7.34 pg/mL versus 58.11±10.75 pg/mL; P <0.05) and secreted protein analysis revealed upregulation of injury‐modifying interleukin‐2, ‐4, ‐10, ‐12, and ‐18 cytokines in the infliximab‐treated cohort. At 4 weeks (n=12), infliximab treatment resulted in significant protective influence, improving left vent...