MTX Treatment Does Not Improve Outcome in Mice with AMI

• Published in: Pharmacology Vol. 106; no. 3-4; p. 225
• Main Authors: Dannenberg, Lisa, Trojovsky, Kajetan, Ayhan, Aysel, Helten, Carolin, Zako, Saif, M'Pembele, René, Mourikis, Philipp, Benkhoff, Marcel, Ignatov, Denis, Sarabhai, Theresia, Petzold, Tobias, Huhn-Wientgen, Ragnar, Zeus, Tobias, Kelm, Malte, Levkau, Bodo, Polzin, Amin
• Format: Journal Article
• Language: English
• Published: Switzerland 01.03.2021
• Subjects: Animals; Blood Cell Count; Blood Platelets - metabolism; Disease Models, Animal; Male; Methotrexate - therapeutic use; Mice; Mice, Inbred C57BL; Myocardial Infarction - blood; Myocardial Infarction - drug therapy; Myocardial Infarction - pathology; Serum Amyloid P-Component - metabolism; Systole; Treatment Outcome; Ventricular Function, Left - drug effects; Infarct size; Mouse model; Cardiovascular inflammation reduction trial; Acute myocardial infarction; Methotrexate
• ISSN: 1423-0313
• DOI: 10.1159/000511279

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. 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. 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 (24hejection 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 × 103/mm3 vs. MTX 1,920 ± 68.68 × 103/mm3, p < 0.0001). White blood cell and RBC as well as rate of monocytes, granulocytes, lymphocytes, and serum amyloid P levels were equal. 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.