Published online before print September 30, 2004, doi: 10.1161/01.ATV.0000146532.98235.e6
© 2004 American Heart Association, Inc.
Atherosclerosis and Lipoproteins |
Differential Expression Patterns of Proinflammatory and Antiinflammatory Mediators During Atherogenesis in Mice
From the Division of Cardiology, Foundation for Medical Research, University Hospital, Geneva, Switzerland.
Correspondence to François Mach, MD, Division of Cardiology, Department of Medicine, University Hospital, Geneva, Foundation for Medical Research, 64 Avenue Roseraie, 1211 Geneva, Switzerland. E-mail Francois.Mach{at}medecine.unige.ch
Objective— Recent advances support the current view of atherosclerosis as an inflammatory process that initiates and promotes lesion development to the point of acute thrombotic complications and clinical events. ApoE-deficient mice are a valuable model for studying the involvement of inflammatory mediators during atherogenesis. In this study, we investigated the correlation between atherosclerotic plaque development and expression of important pro- and antiinflammatory mediators during progression of atherosclerosis in ApoE–/– mice.
Methods and Results— Expression of proinflammatory cytokines, chemokines, and chemokine receptors within aortic lesions increased during atherogenesis, as detected by real-time quantitative reverse-transcription polymerase chain reaction. In parallel, the number of inflammatory cells within lesions increased together with serum cholesterol and body weight. Interestingly, the majority of inflammatory mediators investigated reached their maximum expression values at 10 weeks of diet, followed by continuous decrease of their expression levels, whereas atherosclerotic plaque size further increased. We show that the expression pattern of these different inflammatory mediators mainly correlates with the amount of inflammatory cells present within the atherosclerotic lesions.
Conclusion— Atherosclerosis might result from an imbalance between pro- and antiinflammatory mediators in response to endothelial injury induced by cholesterol-rich diet. These data provide important information on the expression kinetics of inflammatory mediators and point out the possible role of antiinflammatory cells during atherogenesis.
Despite further increase of atherosclerotic lesion size in ApoE–/– mice after 10 weeks of diet, expression of important pro- and antiinflammatory mediators did not further increase or even decreased. These results could be correlated with the amount of inflammatory cells present within atherosclerotic lesions.
Key Words: atherogenesis • inflammation • cytokines • chemokines
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