Aspirin regulates expression and function of scavenger receptor-BI in macrophages: studies in primary human macrophages and in mice.
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
Ivan
I
Department of Internal Medicine, Innsbruck Medical University, Anichstrasse 35, Innsbruck 6020, Austria.
Wehinger
Andreas
A
Schgoer
Wilfried
W
Eller
Philipp
P
Cuzzocrea
Salvatore
S
Foeger
Bernhard
B
Patsch
Josef R
JR
Ritsch
Andreas
A
D000818:Animals; D001241:Aspirin / Q000494:pharmacology*; D001692:Biological Transport; D002460:Cell Line; D002478:Cells, Cultured; D005452:Fluoresceins; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D008075:Lipoproteins, HDL / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D009000:Monocytes / Q000187:drug effects / Q000502:physiology; D047493:PPAR alpha / Q000172:deficiency / Q000235:genetics; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D051122:Scavenger Receptors, Class B / Q000235:genetics* / Q000378:metabolism*
D005452:Fluoresceins; D008075:Lipoproteins, HDL; D047493:PPAR alpha; D012333:RNA, Messenger; C495124:SCARB1 protein, human; C454739:Scarb1 protein, mouse; D051122:Scavenger Receptors, Class B; D011451:Prostaglandin-Endoperoxide Synthases; D001241:Aspirin; C007740:fluorexon