Review Article
Protective Effects of Methotrexate against Proatherosclerotic Cytokines: A Review of the Evidence
Table 2
Effects of methotrexate, adenosine, AICAR, and AMPK activation on endothelial function and vascular homeostasis.
| Mediator | Reported effects |
| Methotrexate | Release of soluble TNF-α receptor p75 ↑ | TNF-α expression/concentrations ↓ | IL-6 expression/concentrations ↓ | ICAM-1 expression ↓ | VCAM-1 expression ↓ | eNOS activity ↑ | Endothelium-dependent vasodilatation ↑ | Mitochondrial mass, membrane potential, and intracellular ATP concentrations ↑ |
| Adenosine | TNF-α expression/concentrations ↓ | IL-6 expression/concentrations ↓ | ICAM-1 expression ↓ | VCAM-1 expression ↓ | E-selectin expression ↓ | eNOS activity ↑ | Blood pressure ↓ | Mitochondrial mass, membrane potential, and intracellular ATP concentrations ↑ | Formation of atherosclerotic lesions ↓ | Cholesterol concentrations ↓ | Triglyceride concentrations ↓ |
| AICAR/AMPK | IL-1 expression/concentrations ↓ | IL-6 expression/concentrations ↓ | ICAM-1 expression ↓ | VCAM-1 expression ↓ | NO synthesis ↑ | Endothelium-dependent vasodilation ↑ | Endothelium-independent vasodilation ↑ | Blood pressure ↓ | Oxidative stress ↓ | Endoplasmic reticulum stress ↓ | Manganese superoxide dismutase induction ↑ | NF-κB ↓ | Monocyte adhesion to endothelial cells ↓ | Restenosis ↓ | Cholesterol efflux capacity ↑ | Cellular glucose uptake ↑ | Glycolysis ↑ |
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AICAR: aminoimidazole carboxamide ribonucleotide; AMPK: 5 adenosine monophosphate-activated protein kinase; TNF-α: tumour necrosis factor-alpha; IL-1: interleukin-1; IL-6: interleukin-6; ICAM-1: intercellular adhesion molecule-1; VCAM-1: vascular cell adhesion molecule-1; ATP: adenosine triphosphate; eNOS: endothelial nitric oxide synthase; NF-κB: nuclear factor kappa-light-chain-enhancer of the activated B-cell; NO: nitric oxide; ↑: increase; ↓: decrease.
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