P2Y 12 Inhibition in Murine Myocarditis Results in Reduced Platelet Infiltration and Preserved Ejection Fraction.

Autor: Schmidt SN; Heart Center Freiburg University, Department of Cardiology and Angiology I, Faculty of Medicine, University of Freiburg, 79106 Freiburg, Germany., Reichardt W; University Medical Center Freiburg, Department of Radiology-Medical Physics, Faculty of Medicine, University of Freiburg, 79106 Freiburg, Germany.; German Consortium for Translational Cancer Research (DKTK), 69120 Heidelberg, Germany.; German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany., Kaufmann BA; Department of Cardiology, University Hospital Basel, University of Basel, 4031 Basel, Switzerland., Wadle C; Heart Center Freiburg University, Department of Cardiology and Angiology I, Faculty of Medicine, University of Freiburg, 79106 Freiburg, Germany., von Elverfeldt D; University Medical Center Freiburg, Department of Radiology-Medical Physics, Faculty of Medicine, University of Freiburg, 79106 Freiburg, Germany., Stachon P; Heart Center Freiburg University, Department of Cardiology and Angiology I, Faculty of Medicine, University of Freiburg, 79106 Freiburg, Germany.; Medical Center Mannheim, Department of Cardiology, Medical Faculty Mannheim, Haemostaseology and Medical Intensive Care University Heidelberg University, 68167 Mannheim, Germany., Hilgendorf I; Heart Center Freiburg University, Department of Cardiology and Angiology I, Faculty of Medicine, University of Freiburg, 79106 Freiburg, Germany., Wolf D; Heart Center Freiburg University, Department of Cardiology and Angiology I, Faculty of Medicine, University of Freiburg, 79106 Freiburg, Germany., Heidt T; Heart Center Freiburg University, Department of Cardiology and Angiology I, Faculty of Medicine, University of Freiburg, 79106 Freiburg, Germany., Duerschmied D; Heart Center Freiburg University, Department of Cardiology and Angiology I, Faculty of Medicine, University of Freiburg, 79106 Freiburg, Germany.; Medical Center Mannheim, Department of Cardiology, Medical Faculty Mannheim, Haemostaseology and Medical Intensive Care University Heidelberg University, 68167 Mannheim, Germany., Peter K; Baker Heart & Diabetes Institute, Melbourne, VIC 3004, Australia., Bode C; Heart Center Freiburg University, Department of Cardiology and Angiology I, Faculty of Medicine, University of Freiburg, 79106 Freiburg, Germany., von Zur Mühlen C; Heart Center Freiburg University, Department of Cardiology and Angiology I, Faculty of Medicine, University of Freiburg, 79106 Freiburg, Germany., Maier A; Heart Center Freiburg University, Department of Cardiology and Angiology I, Faculty of Medicine, University of Freiburg, 79106 Freiburg, Germany.
Jazyk: angličtina
Zdroj: Cells [Cells] 2021 Dec 04; Vol. 10 (12). Date of Electronic Publication: 2021 Dec 04.
DOI: 10.3390/cells10123414
Abstrakt: Previous mouse studies have shown the increased presence of platelets in the myocardium during early stages of myocarditis and their selective detection by MRI. Here, we aimed to depict early myocarditis using molecular contrast-enhanced ultrasound of activated platelets, and to evaluate the impact of a P2Y 12 receptor platelet inhibition. Experimental autoimmune myocarditis was induced in BALB/c mice by subcutaneous injection of porcine cardiac myosin and complete Freund adjuvant (CFA). Activated platelets were targeted with microbubbles (MB) coupled to a single-chain antibody that binds to the "ligand-induced binding sites" of the GPIIb/IIIa-receptor (=LIBS-MB). Alongside myocarditis induction, a group of mice received a daily dose of 100 g prasugrel for 1 month. Mice injected with myosin and CFA had a significantly deteriorated ejection fraction and histological inflammation on day 28 compared to mice only injected with myosin. Platelets infiltrated the myocardium before reduction in ejection fraction could be detected by echocardiography. No selective binding of the LIBS-MB contrast agent could be detected by either ultrasound or histology. Prasugrel therapy preserved ejection fraction and significantly reduced platelet aggregates in the myocardium compared to mice without prasugrel therapy. Therefore, P2Y 12 inhibition could be a promising early therapeutic target in myocarditis, requiring further investigation.
Databáze: MEDLINE
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