Quercitrin treatment protects endothelial progenitor cells from oxidative damage via inducing autophagy through extracellular signal-regulated kinase.
Atherosclerosis is a disease resulting from impaired endothelial function, often caused by oxidant injury or inflammation. Endothelial progenitor cells (EPCs) play a critical role in repairing damaged endothelium and protecting against atherosclerosis. Quercitrin, a plant-derived flavonoid compound, displays antioxidant and anti-inflammatory activities. In this study, we showed that quercitrin treatment reduced the apoptosis of EPCs caused by oxidized low-density lipoprotein (ox-LDL) in a dose-dependent manner. Quercitrin improved tube formation, migration and adhesion of ox-LDL-treated EPCs. To determine the effect of quercitrin in vivo, EPCs treated with or without ox-LDL and quercitrin were locally injected into the ischemic hind limb muscle of nude mice. Those injected with EPCs treated with ox-LDL and quercitrin showed significantly increased local accumulation of EPCs, blood flow recovery and capillary density compared with the control and ox-LDL only groups. Furthermore, we showed that quercitrin enhanced autophagy and upregulated mitogen-activated protein kinase and ERK phosphorylation in a dose-dependent manner in vitro. Autophagy inhibitors, chloroquine and 3-methyladenine, abrogated quercitrin-enhanced autophagy caused by ox-LDL as evidenced by decreased numbers of branch points, migratory cells and adherent cells, and increased numbers of apoptotic cells. The ERK inhibitor PD98059 abrogated quercitrin-enhanced autophagy, as identified by decreased autophagosome formation and downregulated ERK phosphorylation. The inhibition of ERK did not affect the expression of Rac1, but enhanced phosphorylation of Akt. Quercitrin treatment also increased the expression of E-cadherin, and PD98059 abrogated the upregulation of E-cadherin induced by quercitrin. Our findings suggested that autophagy is a protective mechanism in EPCs exposed to oxidative damage. Quercitrin can promote autophagy through the activation of ERK and the ERK signaling pathway is therefore thought to play a pivotal role in mediating the protective effects on EPCs.
['Zhi|Kangkang|K|', 'Li|Maoquan|M|', 'Bai|Jun|J|', 'Wu|Yongfa|Y|', 'Zhou|Sili|S|', 'Zhang|Xiaoping|X|', 'Qu|Lefeng|L|']
D000818:Animals D000975:Antioxidants D001343:Autophagy D002478:Cells, Cultured D004305:Dose-Response Relationship, Drug D066026:Endothelial Progenitor Cells D005121:Extremities D005419:Flavonoids D007511:Ischemia D008077:Lipoproteins, LDL D020935:MAP Kinase Signaling System D008297:Male D051379:Mice D008807:Mice, Inbred BALB C D008819:Mice, Nude D018919:Neovascularization, Physiologic D018384:Oxidative Stress D047428:Protein Kinase Inhibitors D011794:Quercetin
Quercitrin Oxidative damage Autophagy Endothelial progenitor cells (EPCs) ERK signaling pathway