Cyclooxygenase-2 inhibition increases lipopolysaccharide-induced atherosclerosis in mice
| Autor: | Jonathan M. Gitlin, Charles D. Loftin |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2008 |
| Předmět: |
Apolipoprotein E
Lipopolysaccharides Male Lipopolysaccharide Physiology Prostaglandin Inflammation Pharmacology Dinoprostone chemistry.chemical_compound Mice Apolipoproteins E Physiology (medical) medicine Macrophage Animals Porphyromonas gingivalis Sulfonamides biology Cyclooxygenase 2 Inhibitors Tumor Necrosis Factor-alpha Original Articles biology.organism_classification Atherosclerosis Toll-Like Receptor 2 Mice Inbred C57BL Toll-Like Receptor 4 chemistry Celecoxib Cyclooxygenase 2 Immunology biology.protein Macrophages Peritoneal Pyrazoles lipids (amino acids peptides and proteins) Tumor necrosis factor alpha Cyclooxygenase medicine.symptom Cardiology and Cardiovascular Medicine |
| Popis: | Aims The risk of adverse cardiovascular events in humans is increased with chronic use of cyclooxygenase-2 (COX-2) inhibitors. However, the role of COX-2 in animal models of cardiovascular disease has been controversial. In humans and animal models, cardiovascular disease is increased by bacterial infection of the supporting tissue of the teeth, a condition known as periodontal disease. Periodontal disease may result in chronic exposure to pro-inflammatory mediators, such as bacterial lipopolysaccharide (LPS), thereby producing a systemic inflammatory response. The current study examined the role of COX-2 in atherosclerosis induced by LPS derived from the periodontal disease pathogen Porphyromonas gingivalis ( P . gingivalis ). Methods and results Porphyromonas gingivalis LPS was administered by chronic infusion for 28 days and atherosclerosis development was examined in the aortic root of ApoE (apolipoprotein E)-deficient mice. The extent of atherosclerosis was compared between mice receiving control diet or diet containing the COX-2 inhibitor celecoxib. The role of COX-2 in P . gingivalis LPS-induced inflammatory cell activation was examined in peritoneal macrophages. Porphyromonas gingivalis LPS infusion significantly increased atherosclerosis development. In mice infused with P . gingivalis LPS, administration of the COX-2 inhibitor celecoxib further increased the extent of atherosclerotic lesion area. In peritoneal macrophages, P . gingivalis LPS increased the expression of COX-2 mRNA (messenger ribonucleic acid) and the production of prostaglandin (PG) E2 (PGE2), the latter of which was inhibited by celecoxib. Porphyromonas gingivalis LPS-induced expression of tumour necrosis factor alpha (TNFα) was enhanced by inactivation of COX-2 and was attenuated by treatment with PGE2. Conclusion The inhibition of COX-2-derived PGE2 may enhance P . gingivalis LPS-induced atherosclerosis by increasing macrophage production of TNFα. |
| Databáze: | OpenAIRE |
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