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

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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 2005
Externally publishedYes

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Apolipoproteins E
Cyclooxygenase 2
Inbred C57BL Mouse
Atherosclerosis
Macrophages
Prostaglandin-Endoperoxide Synthases
Atherogenic Diet
Chemokine CCL2
Indomethacin
Aorta
Anti-Inflammatory Agents
Tumor Necrosis Factor-alpha

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

Cite this

Burleigh, M. E., Babaev, V. R., Yancey, P. G., Major, A. S., McCaleb, J. L., Oates, J. A., ... 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

Cyclooxygenase-2 promotes early atherosclerotic lesion formation in ApoE-deficient and C57BL/6 mice. / Burleigh, Michael E.; Babaev, Vladimir R.; Yancey, Patricia G.; Major, Amy S.; McCaleb, Jennifer L.; Oates, John A.; Morrow, Jason D.; Fazio, Sergio; Linton, MacRae F.

In: Journal of Molecular and Cellular Cardiology, Vol. 39, No. 3, 09.2005, p. 443-452.

Research output: Contribution to journalArticle

Burleigh, ME, Babaev, VR, Yancey, PG, Major, AS, McCaleb, JL, Oates, JA, Morrow, JD, Fazio, S & Linton, MF 2005, 'Cyclooxygenase-2 promotes early atherosclerotic lesion formation in ApoE-deficient and C57BL/6 mice', Journal of Molecular and Cellular Cardiology, vol. 39, no. 3, pp. 443-452. https://doi.org/10.1016/j.yjmcc.2005.06.011
Burleigh, Michael E. ; Babaev, Vladimir R. ; Yancey, Patricia G. ; Major, Amy S. ; McCaleb, Jennifer L. ; Oates, John A. ; Morrow, Jason D. ; Fazio, Sergio ; Linton, MacRae F. / Cyclooxygenase-2 promotes early atherosclerotic lesion formation in ApoE-deficient and C57BL/6 mice. In: Journal of Molecular and Cellular Cardiology. 2005 ; Vol. 39, No. 3. pp. 443-452.
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AU - Major, Amy S.

AU - McCaleb, Jennifer L.

AU - Oates, John A.

AU - Morrow, Jason D.

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