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Abstract: Background: We recently showed that aspirin promotes scavenger receptor class-B type I (SR-BI) protein expression in vitro in primary human macrophages and in vivo in resident peritoneal macrophages of mice. Methods: We compared SR-BI and CD68 expression in carotid atherosclerotic specimens from endarterectomized patients with (n =38) or without (n =19) low-dose aspirin medication (100mg/day) prior to endarterectomy. Results: We found no differences concerning expression of CD68, indicating that aspirin did not influence macrophage content within atherosclerotic plaques. However, aspirin increased the expression of SR-BI protein in the analyzed specimens. In human THP-1-derived macrophages, induction of SR-BI protein by aspirin was abrogated by concomitant pharmacological inhibition of nuclear factor-kappa B (NF-κB). In in vitro experiments employing cultured primary macrophages from NF-κB/p50 KO mice, aspirin was not able to influence SR-BI expression. Additionally, no considerable effects on SR-BI expression were observed in vivo in resident macrophages of NF-κB/p50 KO mice orally treated with low or high doses of aspirin, respectively. Conclusions: We suggest that aspirin treatment might lead to enhanced expression of SR-BI in human plaque macrophages and that this effect is dependent on the presence of NF-κB. [Copyright &y& Elsevier]

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-α 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-α independent way, suggesting a novel pharmacologic effect of aspirin. [ABSTRACT FROM AUTHOR]