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

    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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  • Cite this

    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