Details

Autor(en) / Beteiligte

• 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.

Titel

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

Ist Teil von

• Journal of molecular and cellular cardiology, 2005-09, Vol.39 (3), p.443-452

Ort / Verlag

England: Elsevier Ltd

Erscheinungsjahr

2005

Quelle

MEDLINE

Beschreibungen/Notizen

• 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.