Quercetin Suppresses the Progression of Atherosclerosis by Regulating MST1-Mediated Autophagy in ox-LDL-Induced RAW264.7 Macrophage Foam Cells

Int J Mol Sci. 2019 Dec 3;20(23):6093. doi: 10.3390/ijms20236093.


Objective: To investigate the process by which quercetin suppresses atherosclerosis by upregulating MST1-mediated autophagy in RAW264.7 macrophages.

Methods: An in vitro foam cell model was established by culturing RAW264.7 macrophages with oxidized low-density lipoprotein (ox-LDL). The cells were treated with quercetin alone or in combination with the autophagy inhibitor, 3-methyladenine, and autophagy agonist, rapamycin. Cell viability was detected with a CCK-8 kit. Lipid accumulation was detected by oil red O staining, senescence was detected by SA-β-gal (senescence-associated β-galactosidase) staining, reactive oxygen species were detected by ROS assay kit. Autophagosomes and mitochondria were detected by transmission electron microscope (TEM), and expression of MST1, LC3-II/I, Beclin1, Bcl-2, P21, and P16 were detected by immunofluorescence and Western blot.

Results: Ox-LDL induced RAW264.7 macrophage-derived foam cell formation, reduced survival, aggravated cell lipid accumulation, and induced a senescence phenotype. This was accompanied by decreased formation of autophagosome; increased expression of P53, P21, and P16; and decreased expression of LC3-II/I and Beclin1. After intervention with quercetin, the cell survival rate was increased, and lipid accumulation and senescence phenotype were reduced. Furthermore, the expression of LC3-II/I and Beclin1 were increased, which was consistent with the ability of quercetin to promote autophagy. Ox-LDL also increased the expression of MST1, and this increase was blocked by quercetin, which provided a potential mechanism by which quercetin may protect foam cells against age-related detrimental effects.

Conclusion: Quercetin can inhibit the formation of foam cells induced by ox-LDL and delay senescence. The mechanism may be related to the regulation of MST1-mediated autophagy of RAW264.7 cells.

Keywords: RAW264.7; atherosclerosis; autophagy; quercetin; senescence.

MeSH terms

  • Adenine / analogs & derivatives
  • Adenine / pharmacology
  • Animals
  • Atherosclerosis / pathology*
  • Autophagy / drug effects*
  • Cell Survival / drug effects
  • Cellular Senescence / drug effects
  • Cyclin-Dependent Kinase Inhibitor p16 / metabolism
  • Cyclin-Dependent Kinase Inhibitor p21 / metabolism
  • Disease Progression*
  • Foam Cells / drug effects
  • Foam Cells / metabolism*
  • Foam Cells / pathology*
  • Hepatocyte Growth Factor / metabolism*
  • Lipid Metabolism / drug effects
  • Lipoproteins, LDL / pharmacology*
  • Mice
  • Proto-Oncogene Proteins / metabolism*
  • Quercetin / pharmacology*
  • RAW 264.7 Cells
  • Sirolimus / pharmacology
  • Up-Regulation / drug effects


  • Cyclin-Dependent Kinase Inhibitor p16
  • Cyclin-Dependent Kinase Inhibitor p21
  • Lipoproteins, LDL
  • Proto-Oncogene Proteins
  • macrophage stimulating protein
  • oxidized low density lipoprotein
  • 3-methyladenine
  • Hepatocyte Growth Factor
  • Quercetin
  • Adenine
  • Sirolimus