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Epigallocatechin gallate protects against homocysteine-induced vascular smooth muscle cell proliferation

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Abstract

Epigallocatechin gallate (EGCG), a bioactive ingredient of green tea, plays a protective role in the cardiovascular system. Homocysteine (Hcy) is a major risk factor for chronic kidney disease and cardiovascular disease. The present study aimed to investigate the role of EGCG in Hcy-induced proliferation of vascular smooth muscle cells (VSMCs) and its underlying mechanism. We also explored the roles of rennin-angiotensin system (RAS), extracellular signal-regulated kinases (ERK1/2), and p38 mitogen-activated protein kinase (p38 MAPK) in this process. Human aortic smooth muscle cells (HASMCs) were treated with different drugs for different periods. The proliferation rate of HASMCs was detected using the CCK-8 and BrdU labeling assays. The Western blot assay was used to determine the expression levels of angiotensin II type 1 receptor (AT-1R), ERK1/2, and p38 MAPK. Compared with the control group, the HASMCs treated with Hcy at different doses (100, 200, 500, and 1000 µM) showed significantly increased proliferation. Hcy increased the expression of AT-1R, whereas EGCG decreased the protein expression of AT-1R. Furthermore, we found that Hcy-induced expression of p-ERK1/2 and p-p38MAPK was dependent on AT-1R. Compared with Hcy (500 µM)-treated cells, EGCG (20 µM)-treated cells showed decreased proliferation as well as expression of AT-1R, p-ERK1/2, and p-p38MAPK. In addition, HASMC proliferation was suppressed by the addition of an AT-1R blocker (olmesartan), an ERK1/2 inhibitor (PD98059), and a p38MAPK inhibitor (SB202190). EGCG can inhibit AT-1R and affect ERK1/2 and p38MAPK signaling pathways, resulting in the decrease of VSMC proliferation induced by Hcy.

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Acknowledgements

This study was supported by the Outstanding Young Training Program of the Pudong Health Bureau of Shanghai (PWRq2014-05), the Key Specialized Construction Project in Medicine of Shanghai (ZK2015A15), Shanghai science and technology commission (15ZR1437400), and the Outstanding Leaders Training Program of the Pudong Health Bureau of Shanghai (PWRI2012-05). All authors have approved the final version of the manuscript and have agreed to submit it to this journal.

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  1. Xiao Li Zhan and Xiu Hong Yang have contributed equally to this paper.

Authors and Affiliations

  1. Division of Nephrology, Pudong Medical Center, Shanghai Pudong Hospital, Fudan University, 2800 Gong Wei Road, Shanghai, China

    Xiao Li Zhan, Xiu Hong Yang, Yan Hong Gu & Hui Min Jin

  2. Hemodialysis Center, Bao Shan Branch of No. 1, People’s Hospital, Shanghai Jiao Tong University, Shanghai, China

    Li Li Guo

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  1. Xiao Li Zhan
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Zhan, X.L., Yang, X.H., Gu, Y.H. et al. Epigallocatechin gallate protects against homocysteine-induced vascular smooth muscle cell proliferation. Mol Cell Biochem 439, 131–140 (2018). https://doi.org/10.1007/s11010-017-3142-6

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