Protective Effects of Methotrexate against Proatherosclerotic Cytokines: A Review of the Evidence
There is good epidemiological evidence that patients with autoimmune rheumatic disease states, particularly rheumatoid arthritis, have an increased risk of cardiovascular morbidity and mortality when compared to the general population. The presence of a chronic systemic proinflammatory state in this...
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| Format: | Article |
| Language: | English |
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Wiley
2017-01-01
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| Series: | Mediators of Inflammation |
| Online Access: | http://dx.doi.org/10.1155/2017/9632846 |
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| author | Arduino A. Mangoni Angelo Zinellu Salvatore Sotgia Ciriaco Carru Matteo Piga Gian Luca Erre |
| author_facet | Arduino A. Mangoni Angelo Zinellu Salvatore Sotgia Ciriaco Carru Matteo Piga Gian Luca Erre |
| author_sort | Arduino A. Mangoni |
| collection | DOAJ |
| description | There is good epidemiological evidence that patients with autoimmune rheumatic disease states, particularly rheumatoid arthritis, have an increased risk of cardiovascular morbidity and mortality when compared to the general population. The presence of a chronic systemic proinflammatory state in this patient group disrupts the structural and functional integrity of the endothelium and the arterial wall, favouring the onset and progression of atherosclerosis. A significant role in the detrimental effects of inflammation on endothelial function and vascular homeostasis is played by specific proatherosclerotic cytokines such as tumour necrosis factor-alpha (TNF-α), interleukin-1 (IL-1), and interleukin-6 (IL-6). Recent systematic reviews and meta-analyses have shown that treatment with methotrexate, a first-line disease-modifying antirheumatic drug (DMARD), is associated with a significant reduction in atherosclerosis-mediated cardiovascular events, such as myocardial infarction and stroke, and mortality, when compared to other DMARDs. This suggests that methotrexate might exert specific protective effects against vascular inflammation and atherosclerosis in the context of autoimmune rheumatic disease. This review discusses the available evidence regarding the potential antiatherosclerotic effects of methotrexate through the inhibition of TNF-α, IL-1, and IL-6 and provides suggestions for future experimental and human studies addressing this issue. |
| format | Article |
| id | doaj-art-6bae9b337165415c8b933f85bf979d69 |
| institution | OA Journals |
| issn | 0962-9351 1466-1861 |
| language | English |
| publishDate | 2017-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Mediators of Inflammation |
| spelling | doaj-art-6bae9b337165415c8b933f85bf979d692025-08-20T02:06:07ZengWileyMediators of Inflammation0962-93511466-18612017-01-01201710.1155/2017/96328469632846Protective Effects of Methotrexate against Proatherosclerotic Cytokines: A Review of the EvidenceArduino A. Mangoni0Angelo Zinellu1Salvatore Sotgia2Ciriaco Carru3Matteo Piga4Gian Luca Erre5Department of Clinical Pharmacology, College of Medicine and Public Health, Flinders Medical Centre, Flinders University, Adelaide, SA, AustraliaDepartment of Biomedical Sciences, University of Sassari, Sassari, ItalyDepartment of Biomedical Sciences, University of Sassari, Sassari, ItalyDepartment of Biomedical Sciences, University of Sassari, Sassari, ItalyRheumatology Unit, University Clinic and AOU of Cagliari, Cagliari, ItalyRheumatology Unit, Department of Clinical and Experimental Medicine, University Hospital of Sassari (AOUSS), Sassari, ItalyThere is good epidemiological evidence that patients with autoimmune rheumatic disease states, particularly rheumatoid arthritis, have an increased risk of cardiovascular morbidity and mortality when compared to the general population. The presence of a chronic systemic proinflammatory state in this patient group disrupts the structural and functional integrity of the endothelium and the arterial wall, favouring the onset and progression of atherosclerosis. A significant role in the detrimental effects of inflammation on endothelial function and vascular homeostasis is played by specific proatherosclerotic cytokines such as tumour necrosis factor-alpha (TNF-α), interleukin-1 (IL-1), and interleukin-6 (IL-6). Recent systematic reviews and meta-analyses have shown that treatment with methotrexate, a first-line disease-modifying antirheumatic drug (DMARD), is associated with a significant reduction in atherosclerosis-mediated cardiovascular events, such as myocardial infarction and stroke, and mortality, when compared to other DMARDs. This suggests that methotrexate might exert specific protective effects against vascular inflammation and atherosclerosis in the context of autoimmune rheumatic disease. This review discusses the available evidence regarding the potential antiatherosclerotic effects of methotrexate through the inhibition of TNF-α, IL-1, and IL-6 and provides suggestions for future experimental and human studies addressing this issue.http://dx.doi.org/10.1155/2017/9632846 |
| spellingShingle | Arduino A. Mangoni Angelo Zinellu Salvatore Sotgia Ciriaco Carru Matteo Piga Gian Luca Erre Protective Effects of Methotrexate against Proatherosclerotic Cytokines: A Review of the Evidence Mediators of Inflammation |
| title | Protective Effects of Methotrexate against Proatherosclerotic Cytokines: A Review of the Evidence |
| title_full | Protective Effects of Methotrexate against Proatherosclerotic Cytokines: A Review of the Evidence |
| title_fullStr | Protective Effects of Methotrexate against Proatherosclerotic Cytokines: A Review of the Evidence |
| title_full_unstemmed | Protective Effects of Methotrexate against Proatherosclerotic Cytokines: A Review of the Evidence |
| title_short | Protective Effects of Methotrexate against Proatherosclerotic Cytokines: A Review of the Evidence |
| title_sort | protective effects of methotrexate against proatherosclerotic cytokines a review of the evidence |
| url | http://dx.doi.org/10.1155/2017/9632846 |
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