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Background: Inflammatory processes are an integral component of the progression and destabilization of atherosclerotic lesions. Tumor necrosis factor-α (TNF-α) is considered a primary mediator of inflammatory processes. The TNF-α receptor p55 activates the induction of adhesion molecule expression, apoptosis, and resistance to bacterial infection. Methods and Results: In this study, we crossbred p55 receptor deficient mice on an apolipoprotein E -/- background (p55-/- apoE-/-) (n=15) and investigated whether they show differences in terms of plaque composition and plaque stability in advanced atherosclerotic lesions compared to wild type mice (p55+/+ apoE-/-) (n=15) at 50 weeks of age. There was no significant difference in levels of circulating cytokines (TNF-α, IL-6, IFN-gamma), plaque progression, plaque composition or features of plaque destabilization, such as thinning of the fibrous cap, plaque hemorrhage or enhanced calcification in the innominate artery of p55-/- apoE-/- compared to wild type (p55+/+ apoE-/-) mice. Conclusions: Progression and destabilization of advanced atherosclerotic lesions does not seem to be mediated via the TNF-α receptor p55. It is possible that severe hyperlipidemia over an extended period as observed in the present study acts as a too potent inflammatory and atherosclerotic stimulus that depletion of a single cytokine receptor can not alter the rapid course of lesion progression and destabilization.
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