MTX Treatment Does Not Improve Outcome in Mice with AMI.

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 (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.

journal_name

Pharmacology

journal_title

Pharmacology

authors

Dannenberg L,Trojovsky K,Ayhan A,Helten C,Zako S,M'Pembele R,Mourikis P,Benkhoff M,Ignatov D,Sarabhai T,Petzold T,Huhn-Wientgen R,Zeus T,Kelm M,Levkau B,Polzin A

doi

10.1159/000511279

subject

Has Abstract

pub_date

2020-11-20 00:00:00

pages

1-7

eissn

0031-7012

issn

1423-0313

pii

000511279

pub_type

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