Epigallocatechin Gallate (EGCG) Improves Anti-Angiogenic State, Cell Viability, and Hypoxia-Induced Endothelial Dysfunction by Downregulating High Mobility Group Box 1 (HMGB1) in Preeclampsia

Background Preeclampsia (PE) is a serious complication of pregnancy with no effective therapy. This study assessed whether epigallocatechin gallate (EGCG) could reduce the production of anti-angiogenic factors, improve cell viability, and suppress endothelial dysfunction in vitro via regulating high mobility group box 1 (HMGB1) in preeclampsia. Material/Methods Human umbilical vein endothelial cells (HUVECs) grown in conditioned medium from hypoxic JEG-3 cells were used to investigate the effects of EGCG on anti-angiogenic state, cell viability, and markers of endothelial dysfunction. To confirm that EGCG exerted its effects via HMGB1, we also examined the impact of EGCG on anti-angiogenic state, cell viability, and endothelial dysfunction following HMGB1 treatment in vitro. Results EGCG inhibited HMGB1 expression in hypoxic trophoblast cells in a dose-dependent manner. In addition, EGCG relieved anti-angiogenic state and endothelial dysfunction in hypoxic trophoblast cells by downregulating HMGB1. Moreover, EGCG dose-dependently promoted cell proliferation by downregulating HMGB1. Conclusions Taken together, our data show the protective role of EGCG in preeclampsia and revealed EGCG-mediated effects on the production of anti-angiogenic factors, cell viability, and endothelial dysfunction through downregulating HMGB1. These observations suggest that EGCG is a novel therapeutic candidate for preeclampsia.

[1]  Qinghua Li,et al.  Elevated microRNA-125b inhibits cytotrophoblast invasion and impairs endothelial cell function in preeclampsia , 2020, Cell Death Discovery.

[2]  F. Abdi,et al.  Factors effective in the prevention of Preeclampsia:A systematic review. , 2020, Taiwanese journal of obstetrics & gynecology.

[3]  Xiao-Ming Yin,et al.  Role of High-Mobility Group Box-1 in Liver Pathogenesis , 2019, International journal of molecular sciences.

[4]  Iekhsan Othman,et al.  Enlightening the role of high mobility group box 1 (HMGB1) in inflammation: Updates on receptor signalling. , 2019, European journal of pharmacology.

[5]  Xinchun Lin,et al.  Effects of epigallocatechin-3-gallate on the HMGB1/RAGE pathway in PM2.5-exposed asthmatic rats. , 2019, Biochemical and biophysical research communications.

[6]  N. Gagey-Eilstein,et al.  VEGF (Vascular Endothelial Growth Factor) Functionalized Magnetic Beads in a Microfluidic Device to Improve the Angiogenic Balance in Preeclampsia. , 2019, Hypertension.

[7]  S. Khaliq,et al.  Altered expression of vascular endothelial growth factor, vascular endothelial growth factor receptor-1, vascular endothelial growth factor receptor-2, and Soluble Fms-like Tyrosine Kinase-1 in peripheral blood mononuclear cells from normal and preeclamptic pregnancies , 2019, The Chinese journal of physiology.

[8]  L. Duley,et al.  Interventionist versus expectant care for severe pre-eclampsia between 24 and 34 weeks' gestation. , 2018, The Cochrane database of systematic reviews.

[9]  C. Siristatidis,et al.  The role of interleukins in preeclampsia: A comprehensive review , 2018, American journal of reproductive immunology.

[10]  Dandan Shi,et al.  Epigallocatechin gallate enhances treatment efficacy of oral nifedipine against pregnancy‐induced severe pre‐eclampsia: A double‐blind, randomized and placebo‐controlled clinical study , 2018, Journal of clinical pharmacy and therapeutics.

[11]  C. Pepine,et al.  Hypertension in pregnancy: Taking cues from pathophysiology for clinical practice , 2018, Clinical cardiology.

[12]  Y. Li,et al.  Epigallocatechin-3-gallate attenuates neointimal hyperplasia in a rat model of carotid artery injury by inhibition of high mobility group box 1 expression , 2017, Experimental and therapeutic medicine.

[13]  Jinyong Peng,et al.  EGCG protects against homocysteine-induced human umbilical vein endothelial cells apoptosis by modulating mitochondrial-dependent apoptotic signaling and PI3K/Akt/eNOS signaling pathways , 2017, Apoptosis.

[14]  Yongxiang Yin,et al.  Sodium tanshinone IIA sulfonate prevents hypoxic trophoblast‐induced endothelial cell dysfunction via targeting HMGB1 release , 2017, Journal of biochemical and molecular toxicology.

[15]  T. Deneva,et al.  Pathophysiological Role of Adiponectin, Leptin and Asymmetric Dimethylarginine in the Process of Atherosclerosis , 2016, Folia medica.

[16]  A. Okamoto,et al.  HLA-G expression is regulated by miR-365 in trophoblasts under hypoxic conditions. , 2016, Placenta.

[17]  M. Tong,et al.  Increased expression of high mobility group box 1 (HMGB1) in the cytoplasm of placental syncytiotrophoblast from preeclamptic placentae. , 2016, Cytokine.

[18]  S. Austin,et al.  Neurovascular Protective Function of Endothelial Nitric Oxide　- Recent Advances. , 2016, Circulation journal : official journal of the Japanese Circulation Society.

[19]  D. Passali,et al.  Rhinosinusal Inflammation and High Mobility Group Box 1 Protein: A New Target for Therapy , 2016, ORL.

[20]  Yingzi Zhao,et al.  Vascular nitric oxide: Beyond eNOS. , 2015, Journal of pharmacological sciences.

[21]  Guangzhao Yang,et al.  Epigallocatechin-3-Gallate Protects HUVECs from PM2.5-Induced Oxidative Stress Injury by Activating Critical Antioxidant Pathways , 2015, Molecules.

[22]  Jingjing Cai,et al.  Hypoxic Trophoblast HMGB1 Induces Endothelial Cell Hyperpermeability via the TRL-4/Caveolin-1 Pathway , 2014, The Journal of Immunology.

[23]  D. Webb,et al.  Blood Markers of Coagulation, Fibrinolysis, Endothelial Dysfunction and Inflammation in Lacunar Stroke versus Non-Lacunar Stroke and Non-Stroke: Systematic Review and Meta-Analysis , 2013, Cerebrovascular Diseases.

[24]  S. Valent,et al.  [The pathophysiology of preeclampsia in view of the two-stage model]. , 2012, Orvosi hetilap.

[25]  T. Ha,et al.  Epigallocatechin-3-O-Gallate Inhibits the Angiotensin II-Induced Adhesion Molecule Expression in Human Umbilical Vein Endothelial Cell Via Inhibition of MAPK Pathways , 2007, Cellular Physiology and Biochemistry.

[26]  ACOG Practice Bulletin No. 202: Gestational Hypertension and Preeclampsia. , 2019, Obstetrics and gynecology.

[27]  Qingyu Wu,et al.  High-Mobility Group Box 1 From Hypoxic Trophoblasts Promotes Endothelial Microparticle Production and Thrombophilia in Preeclampsia , 2018, Arteriosclerosis, thrombosis, and vascular biology.