%0 Journal Article
%T Infliximab Limits Injury in Myocardial Infarction.
%A Livia C
%A Inglis S
%A Crespo-Diaz R
%A Rizzo S
%A Mahlberg R
%A Bagwell M
%A Hillestad M
%A Yamada S
%A Meenakshi Siddharthan DV
%A Singh RD
%A Li X
%A Arrell DK
%A Stalboerger P
%A Witt T
%A El Sabbagh A
%A Rihal M
%A Rihal C
%A Terzic A
%A Bartunek J
%A Behfar A
%J J Am Heart Assoc
%V 13
%N 9
%D 2024 May 7
%M 38700022
%F 6.106
%R 10.1161/JAHA.123.032172
%X <B>BACKGROUND: </B>The purpose of this study was to investigate a therapeutic approach targeting the inflammatory response and consequent remodeling from ischemic myocardial injury.<BR><B>RESULTS: </B>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 ventricular ejection fraction (53.9%±5.4% versus 36.2%±5.3%; P<0.001) and reducing scar size (8.31%±10.9% versus 17.41%±12.5%; P<0.05).<BR><B>CONCLUSIONS: </B>Profiling of coronary thrombus aspirates in patients with ST-segment-elevation MI revealed highest association for tumor necrosis factor-α in injury risk. Infliximab-mediated immune modulation offers an actionable pathway to alter MI-induced inflammatory response, preserving contractility and limiting adverse structural remodeling.