Why the study?
To determine whether low-dose methotrexate alters peripheral blood mononuclear cell adenosine receptor expression in persons at risk for cardiovascular events.
Does low-dose methotrexate alter peripheral blood mononuclear cell adenosine receptor expression in post-MI patients with type 2 diabetes?
RCT (n=20)
randomized
Does low-dose methotrexate alter peripheral blood mononuclear cell adenosine receptor expression in post-MI patients with type 2 diabetes?
p-value: p=0.06 for A2AR, 0.01 for A3R
Low-dose methotrexate preserves A2AR and downregulates A3R expression in PBMCs, indicating its lack of atheroprotective effect in the CIRT trial was not due to adenosine receptor loss.
No practice change in post-MI T2DM; hypothesis-generating for adenosine receptor modulation by methotrexate.
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).
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Reiss et al. (2022) conducted an RCT in Type 2 diabetes and cardiovascular disease (post-myocardial infarction) (n=20). Low-dose methotrexate vs. Placebo was evaluated on Change in peripheral blood mononuclear cell (PBMC) adenosine receptor expression (A2AR and A3R) (p=0.06 for A2AR, 0.01 for A3R).
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