Infliximab Limits Injury in Myocardial Infarction.

Autor: Livia C; Van Cleve Cardiac Regenerative Medicine Program Mayo Clinic Rochester MN USA.; Mayo Clinic Alix School of Medicine Mayo Clinic Graduate School of Biomedical Sciences Rochester MN USA., Inglis S; Van Cleve Cardiac Regenerative Medicine Program Mayo Clinic Rochester MN USA.; Department of Cardiovascular Medicine Mayo Clinic Rochester MN USA., Crespo-Diaz R; Van Cleve Cardiac Regenerative Medicine Program Mayo Clinic Rochester MN USA.; Department of Cardiovascular Medicine Mayo Clinic Rochester MN USA.; Cardiovascular Division University of Minnesota Minneapolis MN USA., Rizzo S; Van Cleve Cardiac Regenerative Medicine Program Mayo Clinic Rochester MN USA.; Mayo Clinic Alix School of Medicine Mayo Clinic Graduate School of Biomedical Sciences Rochester MN USA., Mahlberg R; Van Cleve Cardiac Regenerative Medicine Program Mayo Clinic Rochester MN USA.; Department of Cardiovascular Medicine Mayo Clinic Rochester MN USA., Bagwell M; Van Cleve Cardiac Regenerative Medicine Program Mayo Clinic Rochester MN USA.; Mayo Clinic Alix School of Medicine Mayo Clinic Graduate School of Biomedical Sciences Rochester MN USA., Hillestad M; Van Cleve Cardiac Regenerative Medicine Program Mayo Clinic Rochester MN USA.; Department of Cardiovascular Medicine Mayo Clinic Rochester MN USA., Yamada S; Van Cleve Cardiac Regenerative Medicine Program Mayo Clinic Rochester MN USA.; Marriott Heart Disease Research Program Mayo Clinic Rochester MN USA.; Department of Cardiovascular Medicine Mayo Clinic Rochester MN USA.; Division of Geriatric & Gerontology Medicine Mayo Clinic Rochester MN USA., Meenakshi Siddharthan DV; Van Cleve Cardiac Regenerative Medicine Program Mayo Clinic Rochester MN USA., Singh RD; Van Cleve Cardiac Regenerative Medicine Program Mayo Clinic Rochester MN USA., Li X; Van Cleve Cardiac Regenerative Medicine Program Mayo Clinic Rochester MN USA., Arrell DK; Van Cleve Cardiac Regenerative Medicine Program Mayo Clinic Rochester MN USA.; Marriott Heart Disease Research Program Mayo Clinic Rochester MN USA.; Department of Molecular Pharmacology & Experimental Therapeutics Mayo Clinic Rochester MN USA., Stalboerger P; Van Cleve Cardiac Regenerative Medicine Program Mayo Clinic Rochester MN USA., Witt T; Van Cleve Cardiac Regenerative Medicine Program Mayo Clinic Rochester MN USA.; Department of Cardiovascular Medicine Mayo Clinic Rochester MN USA., El Sabbagh A; Department of Cardiovascular Medicine Mayo Clinic Rochester MN USA., Rihal M; Van Cleve Cardiac Regenerative Medicine Program Mayo Clinic Rochester MN USA., Rihal C; Department of Cardiovascular Medicine Mayo Clinic Rochester MN USA., Terzic A; Van Cleve Cardiac Regenerative Medicine Program Mayo Clinic Rochester MN USA.; Marriott Heart Disease Research Program Mayo Clinic Rochester MN USA.; Department of Cardiovascular Medicine Mayo Clinic Rochester MN USA.; Department of Molecular Pharmacology & Experimental Therapeutics Mayo Clinic Rochester MN USA.; Department of Clinical Genomics Mayo Clinic Rochester MN USA., Bartunek J; Cardiovascular Center OLV Hospital Aalst Belgium., Behfar A; Van Cleve Cardiac Regenerative Medicine Program Mayo Clinic Rochester MN USA.; Marriott Heart Disease Research Program Mayo Clinic Rochester MN USA.; Department of Cardiovascular Medicine Mayo Clinic Rochester MN USA.; Department of Physiology & Biomedical Engineering Mayo Clinic Rochester MN USA.
Jazyk: angličtina
Zdroj: Journal of the American Heart Association [J Am Heart Assoc] 2024 May 07; Vol. 13 (9), pp. e032172. Date of Electronic Publication: 2024 May 03.
DOI: 10.1161/JAHA.123.032172
Abstrakt: 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 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).
Conclusions: 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.
Databáze: MEDLINE
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