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Resveratrol(RSV), a plant compound, has been reported to act as an antioxidant in many inflammatory conditions; however, its protective effect and mechanism against oxidized LDL (ox-LDL)-induced foam cells formation and apoptosis in macrophages remain unknown.
Treated RAW 264.7 macrophages with ox-LDL or tunicamycin (TM, an ER stress inducer) with or without the pretreatment of RSV or ER stress inhibitor 4-phenylbutyric acid (PBA). Detected the expression of CD36 and ER stress related proteins in each group by quantitative real-time PCR and western blot, apoptosis by TUNEL staining and flow cytometry, foam cell formation by oil red O and Dil-ox-LDL.
In RAW 264.7 macrophages, LDL or TM induced foam cells formation and apoptosis and upregulated CD36 and ER stress related protein. Like PBA, RSV inhibited ox-LDL- or TM-induced activation of ER stress response as assessed by the reduced nuclear translocation of activating transcription factor 6 (ATF-6) and the decreased phosphorylation of protein kinase-like ER kinase (PERK) and eukaryotic translation initiation factor 2α (eIF2α), as well as the downregulation of glucose-regulated protein 78 (GRP-78) and CHOP. Moreover, RSV inhibited ox-LDL uptake by macrophages and CD36 upregulation induced by ox-LDL or TM.
RSV can alleviate the formation and apoptosis of macrophage-derived foam cells by suppressing CD36-mediated ox-LDL uptake and subsequent activation of the ER stress-CHOP pathway.