Quercetin protects against ox‑LDL‑induced injury via regulation of ABCAl, LXR‑α and PCSK9 in RAW264.7 macrophages

Mol Med Rep. 2018 Jul;18(1):799-806. doi: 10.3892/mmr.2018.9048. Epub 2018 May 22.

Abstract

Quercetin is a flavonoid that has anti‑inflammatory, anti‑oxidant and lipid metabolic effects. It has also been reported to reduce the risk of cardiovascular disease. The present study measured the effects of quercetin on the expression of ATP‑binding cassette transporter 1 (ABCAl), ATP‑binding cassette sub‑family G member 1 (ABCG1), liver X receptor‑α (LXR‑α), proprotein convertase subtilisin/kexin type 9 (PCSK9), p53, p21 and p16 induced by oxidized low density lipoprotein (ox‑LDL). RAW264.7 macrophages were exposed to ox‑LDL with or without 20 µmol/l quercetin and cell proliferation and senescence were quantified using β‑gal staining. Superoxide dismutase (SOD), malondialdehyde (MDA) and lipid droplets were measured in the cytoplasm using oil red staining, while intracellular and total cholesterol (TC) were measured using filipin staining and a TC kit. Immunofluorescent studies and western blot analysis were performed to quantify the expression of ABCAl, ABCG1, LXR‑α, PCSK9, p53, p21 and p16. Quercetin increased RAW264.7 cell viability and reduced lipid accumulation, senescence, lipid droplets, intracellular cholesterol and TC. It was concluded that quercetin inhibits ox‑LDL‑induced lipid droplets in RAW264.7 cells by upregulation of ABCAl, ABCG1, LXR‑α and downregulation of PCSK9, p53, p21 and p16.

MeSH terms

  • ATP Binding Cassette Transporter 1 / biosynthesis*
  • Animals
  • Cyclin-Dependent Kinase Inhibitor p16 / biosynthesis
  • Cyclin-Dependent Kinase Inhibitor p21 / biosynthesis
  • Lipoproteins, LDL / metabolism*
  • Liver X Receptors / biosynthesis*
  • Macrophages / metabolism*
  • Macrophages / pathology
  • Mice
  • Proprotein Convertase 9 / biosynthesis*
  • Quercetin / pharmacology*
  • RAW 264.7 Cells
  • Tumor Suppressor Protein p53 / biosynthesis
  • Up-Regulation / drug effects*

Substances

  • ABCA1 protein, mouse
  • ATP Binding Cassette Transporter 1
  • Cyclin-Dependent Kinase Inhibitor p16
  • Cyclin-Dependent Kinase Inhibitor p21
  • Lipoproteins, LDL
  • Liver X Receptors
  • Tumor Suppressor Protein p53
  • oxidized low density lipoprotein
  • Quercetin
  • Pcsk9 protein, mouse
  • Proprotein Convertase 9