Why the study?
Targeting inflammation in coronary artery disease and AMI remains debated, and it is unknown whether long-term MTX treatment improves cardiac outcome in AMI.
Does methotrexate improve postischemic cardiac damage in wild-type mice undergoing acute myocardial infarction?
Does methotrexate improve postischemic cardiac damage in wild-type mice undergoing acute myocardial infarction?
Methotrexate treatment prior to acute myocardial infarction does not reduce infarct size or improve systolic function in a murine model, aligning with the negative clinical findings of the CIRT trial.
Answers are grounded in this paper and cite their sources.
MTX shows no post-AMI benefit in mice; leaves open whether targeted anti-inflammatory strategies merit human trials.
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.
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Dannenberg et al. (2020) studied this question.
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