Methotrexate (MTX) exerts its anti-inflammatory effects partly through A2AR activation, which enhances cholesterol efflux transporter proteins like ATP-binding cassette subfamily A member 1 (ABCA1) and ATP-binding cassette subfamily G member 1 (ABCG1) on macrophages, thereby reducing foam cell formation and atherosclerosis risk. Here, ABCA1 is linked to atherosclerosis.