alexa The select cyclooxygenase-2 inhibitor celecoxib reduced the extent of atherosclerosis in apo E- - mice.
Genetics & Molecular Biology

Genetics & Molecular Biology

Journal of Molecular and Genetic Medicine

Author(s): Jacob S, LauryKleintop L, LanzaJacoby S

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Abstract Many investigators have suggested that immune activation may trigger the atherosclerotic process. The benefits of aspirin in preventing myocardial infarction have been attributed, in part, to its anti-inflammatory effects. Several reports have documented that cyclooxygenase (COX)-2 is up-regulated in human and mouse atherosclerotic lesions. To clarify the role of COX-2 in atherosclerosis, we conducted a study to test whether the COX-2 inhibitor, celecoxib, prevents the development and progression of the atherosclerotic process. We have used the apo E-/- mouse, a relevant animal model of atherosclerosis that develops fibrofatty lesions similar to human atherosclerosis. Treatment of 4-wk old apo E-/- mice with a standard rodent no. 5020 diet supplemented with 900 ppm of celecoxib for 16 wk led to an 81\% reduction in lesion size. The mean lesion area per section (mean +/- SD) of proximal aorta from the apo E-/- mice fed the diet with celecoxib (33,991 +/- 7863 microm2, P < 0.001) was significantly less than that of the untreated apo E-/- mice (183,401 +/- 36,212 microm2). There were no lesions detected in the C57B1/6 mice. Immunohistochemistry of the ileum revealed that there was 80\% reduction in staining for intercellular adhesion molecule and 60\% reduction in staining for vascular cell adhesion molecule in the celecoxib treated mice. The protective effect of celecoxib was not maintained when the mice were switched after feeding the celecoxib-supplemented diet to the control 5020 diet for an additional 10 wk. These findings demonstrate that selective inhibition of the COX-2 enzyme with celecoxib prevented the development of atherosclerotic lesions in the proximal aortas from apo E-/- mice. One of the possible mechanisms is reduction in expression of the endothelial cell adhesion cell molecules intercellular adhesion molecule and vascular cell adhesion molecule, which plays a key role in the recruitment of inflammatory cells during the early stages of atherogenesis. This article was published in J Surg Res and referenced in Journal of Molecular and Genetic Medicine

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