| Treatment with methotrexate inhibits atherogenesis in cholesterol-fed rabbits. | |
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MedLine Citation:
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PMID: 22113347 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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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, ten animals were treated with four, weekly intravenous injections of MTX (4 mg/Kg) and ten with four, 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 twofold. The drug inhibited by 50% macrophage migration into the intima and by 84% the presence of apoptotic cells 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 TNF-α-treated human umbilical vein endothelial cell line (HUVEC), incubation with MTX led to downregulation of 5 pro-inflammatory genes, TNF-α, VAP-1, IL-1β, CXCL2 and TLR2 and to up-regulation 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. |
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Authors:
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Adriana Bulgarelli; Adriana Abalen Martins Dias; Bruno Caramelli; Raul Cavalcante Maranhão |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2011-11-21 |
Journal Detail:
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Title: Journal of cardiovascular pharmacology Volume: - ISSN: 1533-4023 ISO Abbreviation: - Publication Date: 2011 Nov |
Date Detail:
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Created Date: 2011-11-24 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 7902492 Medline TA: J Cardiovasc Pharmacol Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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aLipid Metabolism Laboratory, Heart Institute of the Medical School Hospital (InCor), University of São Paulo, São Paulo, Brazil bDepartment of Clinical and Toxicological Analysis, Faculty of Pharmaceutical Sciences, University of São Paulo, São Paulo, Brazil cLaboratory of Animal Research, A. C. Camargo Hospital, São Paulo, São Paulo, Brazil. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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