MTX Treatment Does Not Improve Outcome in Mice with AMI
| Autor: | Marcel Benkhoff, Bodo Levkau, Aysel Ayhan, Tobias Petzold, Kajetan Trojovsky, Saif Zako, Ragnar Huhn-Wientgen, Philipp Mourikis, Carolin Helten, Lisa Dannenberg, Amin Polzin, Denis Ignatov, René M'Pembele, Tobias Zeus, Theresia Sarabhai, Malte Kelm |
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| Rok vydání: | 2020 |
| Předmět: |
Pharmacology
medicine.medical_specialty business.industry Urology Inflammation General Medicine Infarct size medicine.disease Coronary artery disease medicine.anatomical_structure Murine model White blood cell medicine Platelet Methotrexate Myocardial infarction medicine.symptom business medicine.drug |
| Zdroj: | Pharmacology. 106:225-232 |
| ISSN: | 1423-0313 0031-7012 |
| Popis: | 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 (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. 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. |
| Databáze: | OpenAIRE |
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