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Methotrexate effects on adenosine receptor expression in peripheral monocytes of persons with type 2 diabetes and cardiovascular disease
  1. Allison Bethanne Reiss1,2,
  2. Isaac Teboul2,
  3. Lora Kasselman2,
  4. Saba Ahmed2,
  5. Steven E Carsons1,
  6. Joshua De Leon1
  1. 1 Medicine, NYU Long Island School of Medicine, Mineola, New York, USA
  2. 2 Foundations of Medicine, NYU Long Island School of Medicine, Mineola, New York, USA
  1. Correspondence to Dr Allison Bethanne Reiss, NYU Winthrop Hospital, Mineola, NY 11501, USA; Allison.Reiss{at}NYULangone.org

Abstract

The Cardiovascular Inflammation Reduction Trial (CIRT) was designed to assess whether low-dose methotrexate (LD-MTX) would reduce future cardiac events in patients with metabolic syndrome or type 2 diabetes (T2DM) who are post-myocardial infarction (MI) or have multivessel disease. Our previous work indicates that MTX confers atheroprotection via adenosine A2A receptor (A2AR) activation. In order for A2AR ligation to reduce cardiovascular events, A2AR levels would need to be preserved during MTX treatment. This study was conducted to determine whether LD-MTX alters peripheral blood mononuclear cell (PBMC) adenosine receptor expression in persons at risk for cardiovascular events. Post-MI T2DM CIRT patients were randomized to LD-MTX or placebo (n=10/group). PBMC isolated from blood drawn at enrollment and after 6 weeks were evaluated for expression of adenosine receptors and reverse cholesterol transporters by real-time PCR. Fold change between time points was calculated using factorial analyses of variance. Compared with placebo, the LD-MTX group exhibited a trend toward an increase in A2AR (p=0.06), while A3R expression was significantly decreased (p=0.01) after 6 weeks. Cholesterol efflux gene expression did not change significantly. Persistence of A2AR combined with A3R downregulation indicates that failure of MTX to be atheroprotective in CIRT was not due to loss of adenosine receptors on PBMC (ClinicalTrials.gov identifier: NCT01594333).

  • Myocardial Infarction
  • Inflammation
  • Atherosclerosis

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Footnotes

  • Contributors Conceptualization: ABR and JDL. Methodology: ABR, JDL, SA and SEC. Validation: LK, IT. Formal analysis: LK, IT. Data curation: IT and SA. Writing—original draft preparation: IT, ABR. Writing—review and editing: ABR, JDL and SA. Supervision: ABR. Project administration: ABR, JDL. Funding acquisition: ABR. All authors have read and agreed to the published version of the manuscript.

  • Funding This work was supported by the American Heart Association Grant 16GRNT26430041 (ABR).

  • Competing interests Allison Reiss is an Editorial Board Member and Joshua De Leon is an Associate Editor for the Journal of Investigative Medicine. No other competing interests declared.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.