Quercetin Suppresses the Progression of Atherosclerosis by Regulating MST1-Mediated Autophagy in ox-LDL-Induced RAW264.7 Macrophage Foam Cells.
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.
['Cao|Hui|H|', 'Jia|Qingling|Q|', 'Yan|Li|L|', 'Chen|Chuan|C|', 'Xing|Sanli|S|', 'Shen|Dingzhu|D|']
D000225:Adenine D000818:Animals D050197:Atherosclerosis D001343:Autophagy D002470:Cell Survival D016922:Cellular Senescence D019941:Cyclin-Dependent Kinase Inhibitor p16 D050759:Cyclin-Dependent Kinase Inhibitor p21 D018450:Disease Progression D005487:Foam Cells D017228:Hepatocyte Growth Factor D050356:Lipid Metabolism D008077:Lipoproteins, LDL D051379:Mice D011518:Proto-Oncogene Proteins D011794:Quercetin D000067996:RAW 264.7 Cells D020123:Sirolimus D015854:Up-Regulation
quercetin atherosclerosis autophagy RAW264.7 senescence