EGCG protects vascular endothelial cells from oxidative stress-induced damage by targeting the autophagy-dependent PI3K-AKT-mTOR pathway

Jiao Meng; Yuhua Chen; Junzhe Wang; Junling Qiu; Cuicui Chang; Fangfang Bi; Xiaopeng Wu; Wei Liu

doi:10.21037/atm.2020.01.92

EGCG protects vascular endothelial cells from oxidative stress-induced damage by targeting the autophagy-dependent PI3K-AKT-mTOR pathway

Ann Transl Med. 2020 Mar;8(5):200. doi: 10.21037/atm.2020.01.92.

Authors

Jiao Meng^{1

2}, Yuhua Chen^{1

2}, Junzhe Wang², Junling Qiu², Cuicui Chang², Fangfang Bi^{1

2}, Xiaopeng Wu², Wei Liu²

Affiliations

¹ Central Laboratory of Medicine School, Xi'an Peihua University, Xi'an 710100, China.
² Department of Medical Science Research Center, Shaanxi Fourth People's Hospital, Xi'an 710143, China.

Abstract

Background: Autophagy plays an important role in cellular homeostasis. Epigallocatechin gallate (EGCG), a polyphenol derived from green tea, has been shown to elicit vascular protective effects. Our study aimed to investigate the protective effect of EGCG in an endothelial injury model induced by hydrogen peroxide (H₂O₂) and reveal the possible mechanisms.

Methods: Human vascular endothelial cells (HUVECs) were pretreatment with different concentration of EGCG, then exposed to H₂O₂. Cell viability was measured with MTS assay. Apoptosis was evaluated with TUNEL staining and apoptosis-related protein was determined by western blot. Autophagy flux was assessed by transmission electron microscopy and LC3 plasmid transfection. Besides, the role mTOR in EGCG-mediated antioxidant responses was validated with siRNA transfection.

Results: The results showed that pretreatment with EGCG significantly improved the survival of HUVECs from H₂O₂-induced cell death. After exposed to H₂O₂, EGCG upregulated the levels of Atg5, Atg7, LC3 II/I, and the Atg5-Atg12 complex in HUVECs, while downregulated apoptosis-related protein. Besides, EGCG inhibited the PI3K-AKT-mTOR signaling pathway. Knockdown of mTOR partially promoted EGCG-induced autophagy.

Conclusions: These results suggest that EGCG induces autophagy by targeting the mTOR pathway, indicating that EGCG has the potential to prevent and treat oxidative stress-related cardiovascular diseases.

Keywords: Epigallocatechin gallate (EGCG); autophagy; endothelial cell; mTOR; oxidative stress.