title: Treatment with methotrexate inhibits atherogenesis in cholesterol-fed rabbits.
abstract: A decrease in the number of cardiovascular events in patients with rheumatoid arthritis or psoriasis treated with methotrexate (MTX) has been observed in the literature. The aim of this study was to test whether MTX could promote anti-inflammatory effects and reduce the atherosclerotic lesions in rabbits with atherosclerosis induced by cholesterol feeding. Twenty male New Zealand rabbits were fed a 1% cholesterol diet for 60 days. Starting from day 30 of cholesterol feeding, 10 animals were treated with 4 weekly intravenous injections of MTX (4 mg/kg) and 10 with 4 weekly saline solution injections for 30 days. MTX reduced the size of the lesion areas of cholesterol-fed animals by 75% and intima-media ratio 2-fold. The drug inhibited macrophage migration into the intima by 50% and the presence of apoptotic cells by 84% but did not inhibit the intimal proliferation of smooth muscle cells. MTX treatment also diminished the positive staining area of metalloproteinase 9 in the intima, which is probably beneficial. In the tumor necrosis factor-α-treated human umbilical vein endothelial cell line, incubation with MTX led to downregulation of 5 pro-inflammatory genes, TNF-α, VAP-1, IL-1β, CXCL2, and TLR2, and upregulation of the anti-inflammatory TGF-β1 gene, thus showing endothelium-protective properties. In conclusion, MTX showed direct in vivo anti-atherosclerotic action and may have potential in the treatment of this disorder.
authors: Lipid Metabolism Laboratory, Heart Institute of the Medical School Hospital (InCor), A. C. Camargo Hospital, São Paulo, São Paulo, Brazil.
authors: Adriana
authors: A
authors: Bulgarelli
authors: Adriana Abalen
authors: AA
authors: Martins Dias
authors: Bruno
authors: B
authors: Caramelli
authors: Raul Cavalcante
authors: RC
authors: Maranhão
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D017209:Apoptosis; D050197:Atherosclerosis / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002791:Cholesterol, Dietary / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation / Q000187:drug effects; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D007249:Inflammation / Q000188:drug therapy / Q000473:pathology; D008264:Macrophages / Q000378:metabolism; D008297:Male; D008727:Methotrexate / Q000494:pharmacology*; D032389:Myocytes, Smooth Muscle / Q000187:drug effects / Q000378:metabolism; D011817:Rabbits; D014409:Tumor Necrosis Factor-alpha / Q000008:administration & dosage; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D000893:Anti-Inflammatory Agents; D002791:Cholesterol, Dietary; D014409:Tumor Necrosis Factor-alpha; D008727:Methotrexate