Epigallocatechin Gallate (EGCG) Stimulates Autophagy in Vascular Endothelial Cells

Kim, Hae-Suk; Montana, Vedrana; Jang, Hyun-Ju; Parpura, Vladimir; Kim, Jeong‐A

doi:10.1074/jbc.m113.477505

Cited by 165 publications

(139 citation statements)

References 66 publications

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“…Endostatin, a potent inhibitor of neovascularization and tumor growth, triggers autophagic cell death in the human endothelial cell line EA.hy926 (12). The green tea polyphenol epigallocatechin gallate promotes formation of LC3-II and autophagosomes in primary bovine aortic endothelial cells (13). Moreover, mice harboring endothelial cell-specific silencing of autophagy-related gene 7 (Atg7) manifest normal vessel architecture and capillary density, yet exhibit impaired synthesis and release of von Willebrand factor (vWF), resulting in prolonged bleeding times (14).…”

Section: Autophagy In the Myocardiummentioning

confidence: 99%

Autophagy in cardiovascular biology

Lavandero

Chiong

Rothermel³

et al. 2015

J. Clin. Invest.

280

211

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Autophagy in the vascular systemEndothelial cells. Autophagy can be regulated in vascular endothelial cells by compounds circulating in the bloodstream or localized within the subendothelial layer of atherosclerotic plaque. For example, in cultured HUVECs, vitamin D increases beclin 1, a key comCardiovascular disease is the leading cause of death worldwide. As such, there is great interest in identifying novel mechanisms that govern the cardiovascular response to disease-related stress. First described in failing hearts, autophagy within the cardiovascular system has been widely characterized in cardiomyocytes, cardiac fibroblasts, endothelial cells, vascular smooth muscle cells, and macrophages. In all cases, a window of optimal autophagic activity appears to be critical to the maintenance of cardiovascular homeostasis and function; excessive or insufficient levels of autophagic flux can each contribute to heart disease pathogenesis. In this Review, we discuss the potential for targeting autophagy therapeutically and our vision for where this exciting biology may lead in the future.

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Section: Autophagy In the Myocardiummentioning

confidence: 99%

Autophagy in cardiovascular biology

Lavandero

Chiong

Rothermel³

et al. 2015

J. Clin. Invest.

280

211

View full text Add to dashboard Cite

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“…In addition, the released ectodomain portion of TNFR1 may bind to TNF-α in the extracellular space and neutralize its activity [20]. Although the mechanisms are not completely elucidated, EGCG also increases cytosolic Ca 2+ in vascular smooth muscle cells and endothelial cells by extracellular Ca 2+ influx or release from endoplasmic reticulum (ER) storage Ca 2+ [21][22][23]. Thus, we hypothesized that EGCG may have anti-TNF-α effects by causing ectodomain shedding of TNFR1 through Ca 2+ -dependent activation of ADAM10.…”

Section: Introductionmentioning

confidence: 99%

Epigallocatechin-3-Gallate Attenuates the Effects of TNF-α in Vascular Endothelial Cells by Causing Ectodomain Shedding of TNF Receptor 1

Yang

Moon²,

Lee

et al. 2016

Cell Physiol Biochem

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Background/Aims: We investigated the mechanism underlying anti-tumor necrosis factor-α (TNF-α) effects of epigallocatechin-3-gallate (EGCG) in human aortic endothelial cells. Methods: Tumor necrosis factor receptor 1 (TNFR1) was assessed by Western blot analysis. Cytosolic Ca²⁺ was measured using Fluo-4 AM. A disintegrin and metalloprotease 10 (ADAM10) was localized by immunofluorescence staining. Results: EGCG caused ectodomain shedding of TNFR1 within 30 min and attenuated TNF-α-induced endothelin-1 (ET-1) expression. EGCG-induced TNFR1 ectodomain shedding was prevented by BAPTA-AM (intracellular Ca²⁺ chelator), but not by the absence of extracellular Ca²⁺. In physiologic extracellular Ca²⁺ concentration, EGCG markedly increased cytosolic Ca²⁺. Even in the absence of extracellular Ca²⁺, EGCG raised cytosolic Ca²⁺, though less potently. siRNA depletion of ADAM10 prevented EGCG-induced ectodomain shedding of TNFR1 and also diminished the inhibitory effect of EGCG on TNF-α-induced ET-1 expression. EGCG caused translocation of ADAM10 to the plasma membrane, and this effect was prevented by BAPTA-AM. Besides extracellular Ca²⁺ influx, release of intracellular stored Ca²⁺ caused ADAM10-dependent ectodomain shedding of TNFR1. Conclusion: EGCG decreases the responsiveness of cells to TNF-α by causing ADAM10-dependent ectodomain shedding of TNFR1. This effect was attributed to its property to increase cytosolic Ca²⁺ through both extracellular Ca²⁺ influx and release of stored Ca²⁺.

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“…The induction of autophagy may be involved in the protective effect against SFA-induced lipotoxicity in some cell types, including vascular endothelial cells, hepatocytes, and pancreatic beta-cells (Chen, Sun et al, 2013;Kim, Montana, Jang, Parpura, & Kim, 2013;Li et al, 2014). Therefore, we first determined whether activating autophagy was protective against palmitate-induced cell death in EA.hy926 cells.…”

Section: Sfn Protects Human Umbilical Vein Cells Against Palmitate-inmentioning

confidence: 99%

Sulforaphane protects human umbilical vein cells against lipotoxicity by stimulating autophagy via an AMPK-mediated pathway

Wang

Zhao

Liu

et al. 2015

Journal of Functional Foods

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Epigallocatechin Gallate (EGCG) Stimulates Autophagy in Vascular Endothelial Cells

Cited by 165 publications

References 66 publications

Autophagy in cardiovascular biology

Autophagy in cardiovascular biology

Epigallocatechin-3-Gallate Attenuates the Effects of TNF-α in Vascular Endothelial Cells by Causing Ectodomain Shedding of TNF Receptor 1

Sulforaphane protects human umbilical vein cells against lipotoxicity by stimulating autophagy via an AMPK-mediated pathway

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