Autor: |
Nicholas S Kirkby, Martina H Lundberg, William R Wright, Timothy D Warner, Mark J Paul-Clark, Jane A Mitchell |
Jazyk: |
angličtina |
Rok vydání: |
2014 |
Předmět: |
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Zdroj: |
PLoS ONE, Vol 9, Iss 6, p e98165 (2014) |
Druh dokumentu: |
article |
ISSN: |
1932-6203 |
DOI: |
10.1371/journal.pone.0098165 |
Popis: |
Cyxlo-oxygenase (COX)-2 inhibitors, including traditional nonsteroidal anti-inflammatory drugs (NSAIDs) are associated with increased cardiovascular side effects, including myocardial infarction. We and others have shown that COX-1 and not COX-2 drives vascular prostacyclin in the healthy cardiovascular system, re-opening the question of how COX-2 might regulate cardiovascular health. In diseased, atherosclerotic vessels, the relative contribution of COX-2 to prostacyclin formation is not clear. Here we have used apoE(-/-)/COX-2(-/-) mice to show that, whilst COX-2 profoundly limits atherosclerosis, this protection is independent of local prostacyclin release. These data further illustrate the need to look for new explanations, targets and pathways to define the COX/NSAID/cardiovascular risk axis. Gene expression profiles in tissues from apoE(-/-)/COX-2(-/-) mice showed increased lymphocyte pathways that were validated by showing increased T-lymphocytes in plaques and elevated plasma Th1-type cytokines. In addition, we identified a novel target gene, rgl1, whose expression was strongly reduced by COX-2 deletion across all examined tissues. This study is the first to demonstrate that COX-2 protects vessels against atherosclerotic lesions independently of local vascular prostacyclin and uses systems biology approaches to identify new mechanisms relevant to development of next generation NSAIDs. |
Databáze: |
Directory of Open Access Journals |
Externí odkaz: |
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