Cyclooxygenase-2 inhibition increases lipopolysaccharide-induced atherosclerosis in mice

Jonathan M. Gitlin, Charles D. Loftin

Research output: Contribution to journalArticlepeer-review

57 Scopus citations


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.

Original languageEnglish
Pages (from-to)400-407
Number of pages8
JournalCardiovascular Research
Issue number2
StatePublished - Feb 2009

Bibliographical note

Funding Information:
This work was supported by the National Institutes of Health (P20 RR020145), and C.D.L. is supported by the National Institutes of Health (HL083122).


  • Atherosclerosis
  • Cyclooxygenase
  • Endotoxins
  • Infection/inflammation
  • Macrophages
  • Prostaglandins

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)


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