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(The FASEB Journal. 2006;20:1328-1335.)
© 2006 FASEB

Aspirin regulates expression and function of scavenger receptor-BI in macrophages: studies in primary human macrophages and in mice

Ivan Tancevski*,1, Andreas Wehinger*,1, Wilfried Schgoer*, Philipp Eller*, Salvatore Cuzzocrea{dagger}, Bernhard Foeger*, Josef R. Patsch* and Andreas Ritsch*,2

* Department of Internal Medicine, Innsbruck Medical University, Innsbruck, Austria; and

{dagger} Dipartimento Clinico e Sperimentale di Medicina e di Farmacologia, Centro per lo Studio ed il Trattamento dei Neurolesi Lungodegenti, Facoltà di Medicina e Chirurgia, Università di Messina, Messina, Italy

2Correspondence: Department of Internal Medicine, Innsbruck Medical University, Anichstrasse 35, Innsbruck 6020, Austria. E-mail: andreas.ritsch{at}uibk.ac.at

Scavenger receptor class B type I (SR-BI) has been shown to be expressed in human atherosclerotic plaque macrophages, where it is believed to reduce atherosclerosis by promoting cholesterol efflux. In this study we investigated the influence of aspirin and other NSAIDs on SR-BI expression and function in cultured human macrophages as well as in different mouse strains. Incubation of human macrophages with 0.5 mmol/l aspirin resulted in increased SR-BI protein expression and increased uptake of HDL-associated [3H]cholesteryl oleate without changes of SR-BI mRNA levels. In contrast, using 5 mmol/l of aspirin, SR-BI expression and function were significantly decreased. Sodium salicylate exerted similar effects on SR-BI expression, whereas no effects were observed using known COX1/2 inhibitors ibuprofen and naproxen, respectively. In in vivo studies low-dose aspirin treatment (6 mg/kg·day) induced SR-BI expression in wild-type and PPAR-{alpha} knockout mice, respectively, whereas the opposite effect was observed upon high-dose aspirin treatment (60 mg/kg·day) in these animals. We could show that COX-independent effects of aspirin were able to enhance expression of SR-BI in macrophages in a post-transcriptional, PPAR-{alpha} independent way, suggesting a novel pharmacologic effect of aspirin.—Tancevski, I., Wehinger, A., Schgoer, W., Eller, P., Cuzzocrea, S., Foeger, B., Patsch, J. R., Ritsch, A. Aspirin regulates expression and function of scavenger receptor-BI in macrophages: studies in primary human macrophages and in mice.


Key Words: SR-BI • PPAR-{alpha} • KO mice • NF-{kappa}B







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