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Angiogenesis

, Volume 19, Issue 3, pp 311–324 | Cite as

Quercitrin treatment protects endothelial progenitor cells from oxidative damage via inducing autophagy through extracellular signal-regulated kinase

  • Kangkang Zhi
  • Maoquan Li
  • Jun Bai
  • Yongfa Wu
  • Sili Zhou
  • Xiaoping ZhangEmail author
  • Lefeng QuEmail author
Original Paper

Abstract

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.

Keywords

Autophagy Endothelial progenitor cells (EPCs) Oxidative damage Quercitrin ERK signaling pathway 

Notes

Acknowledgments

This work was supported by the Program of Science and Technology Commission of Shanghai Municipality 13ZR1414500 and 11ZR1433200; the Program of Putuo District Science and Technology Commission of Shanghai, No. B121.

Compliance with ethical standards

Conflict of interest

The authors declare no conflict of interest.

Supplementary material

10456_2016_9504_MOESM1_ESM.tif (754 kb)
Fig. S1 Autophagy inhibitors abrogated quercitrin-enhanced autophagy caused by ox-LDL. After incubation with 200 μg/ml ox-LDL for 2 h, cultured EPCs were treated 40 μM quercitrin for 6 h. (A) LC3-II fluorescent-stained cells and quantification of the number of autophagosomes. (B) Western blot analysis of LC3-I/II and Beclin-1 expression. β-actin was included as a loading control (n=3, *p < 0.05, compared with ox-LDL group; # p < 0.05, compared with 40 μM quercitrin group). (TIFF 753 kb)

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Copyright information

© Springer Science+Business Media Dordrecht 2016

Authors and Affiliations

  1. 1.Department of Vascular and Endovascular SurgeryChangzheng HospitalShanghaiChina
  2. 2.Department of Interventional RadiologyTenth People’s Hospital of Tongji UniversityShanghaiChina
  3. 3.Institute of Intervention VesselTongji UniversityShanghaiChina

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