Cyclooxygenase-2 promotes early atherosclerotic lesion formation in ApoE-deficient and C57BL/6 mice

Michael E. Burleigh, Vladimir R. Babaev, Patricia G. Yancey, Amy S. Major, Jennifer L. McCaleb, John A. Oates, Jason D. Morrow, Sergio Fazio, MacRae F. Linton

Research output: Contribution to journalArticle

86 Scopus citations

Abstract

Cyclooxygenase (COX) 2 is expressed in atherosclerotic lesions. We have previously reported that selective inhibition of COX-2 reduces early atherosclerosis in LDLR deficient mice. To examine the role of COX-2 in atherosclerosis in other mouse models, we studied the effects of selective COX-2 inhibition (by rofecoxib and NS-398) and nonselective COX inhibition (by indomethacin) on early atherosclerotic lesion formation in apolipoprotein E-deficient (apoE-/-) mice. Selective COX-2 and nonselective COX inhibition reduced atherosclerosis in female apoE-/- mice by 35-38% and 38-51% in the proximal and en face aortas, respectively. Next we investigated the role of macrophage COX-2 by transplanting COX-2-/- fetal liver cells into C57BL/6 mice and challenging the mice with an atherogenic diet. Genetic deletion of COX-2 from hematopoietic cells reduced atherosclerosis by 51%. In addition, LPS activated COX-2-/- macrophages had decreased expression of monocyte chemoattractant protein-1 (MCP-1) and tumor necrosis factor-alpha (TNFα). The results demonstrate that selective inhibition of COX-2 and elimination of COX-2 from macrophages significantly reduces early atherosclerotic lesion formation in apoE-deficient and C57BL/6 mice. These results are compatible with COX-2 expression by macrophages having a proatherogenic role, and support the potential of anti-inflammatory therapeutic approaches for atherosclerosis.

Original languageEnglish (US)
Pages (from-to)443-452
Number of pages10
JournalJournal of molecular and cellular cardiology
Volume39
Issue number3
DOIs
StatePublished - Sep 1 2005
Externally publishedYes

Keywords

  • Atherosclerosis
  • Bone marrow transplantation
  • COX-2
  • COX-2 selective inhibitors
  • Cyclooxygenase
  • Cyclooxygenase inhibitors
  • Inflammation
  • Knockout mice
  • Pharmacology
  • Prostaglandins

ASJC Scopus subject areas

  • Molecular Biology
  • Cardiology and Cardiovascular Medicine

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    Burleigh, M. E., Babaev, V. R., Yancey, P. G., Major, A. S., McCaleb, J. L., Oates, J. A., Morrow, J. D., Fazio, S., & Linton, M. F. (2005). Cyclooxygenase-2 promotes early atherosclerotic lesion formation in ApoE-deficient and C57BL/6 mice. Journal of molecular and cellular cardiology, 39(3), 443-452. https://doi.org/10.1016/j.yjmcc.2005.06.011