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Dannenberg, Lisa; Trojovsky, Kajetan; Ayhan, Aysel; Helten, Carolin; Zako, Saif; M'Pembele, Rene; Mourikis, Philipp; Benkhoff, Marcel; Ignatov, Denis; Sarabhai, Theresia; Petzold, Tobias; Huhn-Wientgen, Ragnar; Zeus, Tobias; Kelm, Malte; Levkau, Bodo und Polzin, Amin (2020): MTX Treatment Does Not Improve Outcome in Mice with AMI. In: Pharmacology, Bd. 106: S. 225-231

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Abstract

Background: Targeting inflammation in patients with coronary artery disease and/or acute myocardial infarction (AMI) is a matter of debate. Methotrexate (MTX) is one of the most widely used immunosuppressants. Cardiovascular Inflammation Reduction Trial (CIRT) recently failed to demonstrate reduced cardiovascular events in MTX-treated patients. However, it is not known if long-term MTX treatment improves cardiac outcome in AMI. Therefore, in this study, we investigated the postischemic phase in MTX-treated mice undergoing AMI. Methods: Wild-type mice received MTX medication intraperitoneally for 2 weeks. Afterward, AMI was induced by transient left anterior ascending artery ligation. Postischemic cardiac damage after 24 h was assessed. Results: MTX treatment did not affect infarct size as compared to control (IS/AAR: Con 76.20% +/- 12.37%/AAR vs. MTX 73.51 +/- 11.72%/AAR, p = 0.64). Moreover, systolic function and structural parameters did not differ between groups ((24h)ejection fraction: Con 36.49 +/- 3.23% vs. MTX 32.77 +/- 2.29%, p = 0.41;24hLVID;d: Con 3.57 +/- 0.17 mm vs. MTX 3.19 +/- 0.13 mm, p = 0.14). Platelets were increased by MTX (Con 1,442 +/- 69.20 x 10(3)/mm(3) vs. MTX 1,920 +/- 68.68 x 10(3)/mm(3), p < 0.0001). White blood cell and RBC as well as rate of monocytes, granulocytes, lymphocytes, and serum amyloid P levels were equal. Conclusion: MTX medication did not improve postischemic cardiac damage in a murine model of AMI. Future trials are needed to identify and investigate other anti-inflammatory targets to improve cardiovascular outcome.

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