Role of endothelial‑microparticles and the tissue factor pathway in ginsenoside Rb1‑mediated prevention of umbilical vein endothelial cell injury

Zhao,Miaomiao; Xie,Juan; Shen,Haorui; Wang,Xiaoxiao; Wu,Qiuling; Xia,Linghui

doi:10.3892/br.2020.1384

Role of endothelial‑microparticles and the tissue factor pathway in ginsenoside Rb1‑mediated prevention of umbilical vein endothelial cell injury

Authors:
- Miaomiao Zhao
- Juan Xie
- Haorui Shen
- Xiaoxiao Wang
- Qiuling Wu
- Linghui Xia
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Affiliations: Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430000, P.R. China, The First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin 300000, P.R. China
Published online on: November 6, 2020 https://doi.org/10.3892/br.2020.1384
Article Number: 8
Copyright: © Zhao et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Hepatic veno‑occlusive disease (VOD) is a life‑threatening complication of hematopoietic stem cell transplantation, which urgently requires effective prevention and treatment. Endothelial damage is recognized as the first event in patients with hepatic VOD. However, the mechanism by which endothelial injury induces thrombosis in hepatic VOD is still not clear. In the present study, monocrotaline (MCT) was used to induce endothelial cell injury in EA.hy926 cells to imitate in vitro hepatic VOD. MCT significantly increased apoptosis in EA.hy926 endothelial cells and the secretion of endothelial microparticles (EMPs) which can be used to reflect the level of endothelial injury. Additionally, MCT significantly enhanced the expression of soluble tissue factor (TF) and EMP‑bound TF protein, suggesting that EMPs may participate in the development of hepatic VOD by regulating coagulation. Ginsenoside Rb1, a major constituent and effective ingredient of Panax ginseng, was found to significantly decrease MCT‑induced endothelial injury and release of EMPs. Moreover, Ginsenoside Rb1 decreased soluble TF released by EA.hy926 cells and EMP‑bound TF protein induced by MCT. These data suggest that ginsenoside Rb1 may serve as a potent prophylactic and/or as a treatment of hepatic VOD by protecting endothelial cells and preventing microthrombosis induced by endothelial injury.

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1	Johnson DB and Savani BN: How can we reduce hepatic veno-occlusive disease-related deaths after allogeneic stem cell transplantation? Exp Hematol. 40:513–517. 2012.PubMed/NCBI View Article : Google Scholar
2	Roeker LE, Kim HT, Glotzbecker B, Nageshwar P, Nikiforow S, Koreth J, Armand P, Cutler C, Alyea EP, Antin JH, et al: Early clinical predictors of hepatic Veno-occlusive Disease/sinusoidal obstruction syndrome after myeloablative stem cell transplantation. Biol Blood Marrow Transplant. 25:137–144. 2019.PubMed/NCBI View Article : Google Scholar
3	Dalle JH and Giralt SA: Hepatic Veno-occlusive disease after hematopoietic stem cell transplantation: Risk factors and stratification, prophylaxis, and treatment. Biol Blood Marrow Transplant. 22:400–409. 2016.PubMed/NCBI View Article : Google Scholar
4	Corbacioglu S, Jabbour EJ and Mohty M: Risk Factors for development of and progression of hepatic Veno-occlusive Disease/sinusoidal obstruction syndrome. Biol Blood Marrow Transplant. 25:1271–1280. 2019.PubMed/NCBI View Article : Google Scholar
5	Dignan FL, Wynn RF, Hadzic N, Karani J, Quaglia A, Pagliuca A, Veys P and Potter MN: Haemato-oncology Task Force of British Committee for Standards in Haematology; British Society for Blood and Marrow Transplantation. BCSH/BSBMT guideline: Diagnosis and management of veno-occlusive disease (sinusoidal obstruction syndrome) following haematopoietic stem cell transplantation. Br J Haematol. 163:444–457. 2013.PubMed/NCBI View Article : Google Scholar
6	Corbacioglu S, Carreras E, Mohty M, Pagliuca A, Boelens JJ, Damaj G, Iacobelli M, Niederwieser D, Olavarría E, Suarez F, et al: Defibrotide for the treatment of hepatic Veno-occlusive disease: Final results from the international compassionate-use program. Biol Blood Marrow Transplant. 22:1874–1882. 2016.PubMed/NCBI View Article : Google Scholar
7	Bagal B, Chandrasekharan A, Chougle A and Khattry N: Low, fixed dose defibrotide in management of hepatic Veno-occlusive disease post stem cell transplantation. Hematol Oncol Stem Cell Ther. 11:47–51. 2018.PubMed/NCBI View Article : Google Scholar
8	Cui YC, Pan CS, Yan L, Li L, Hu BH, Chang X, Liu YY, Fan JY, Sun K, Li Q and Han JY: Ginsenoside Rb1 protects against Ischemia/reperfusion-induced myocardial injury via energy metabolism regulation mediated by RhoA signaling pathway. Sci Rep. 7(44579)2017.PubMed/NCBI View Article : Google Scholar
9	Ren S, Leng J, Xu XY, Jiang S, Wang YP, Yan XT, Liu Z, Chen C, Wang Z and Li W: Ginsenoside Rb1, A major saponin from panax ginseng, exerts protective effects against acetaminophen-induced hepatotoxicity in mice. Am J Chin Med. 47:1815–1831. 2019.PubMed/NCBI View Article : Google Scholar
10	Wang J, Qiao L, Li Y and Yang G: Ginsenoside Rb1 attenuates intestinal ischemia-reperfusion-induced liver injury by inhibiting NF-kappaB activation. Exp Mol Med. 40:686–698. 2008.PubMed/NCBI View Article : Google Scholar
11	Ke L, Guo W, Xu J, Zhang G, Wang W and Huang W: Ginsenoside Rb1 attenuates activated microglia-induced neuronal damage. Neural Regen Res. 9:252–259. 2014.PubMed/NCBI View Article : Google Scholar
12	Xu Z, Lan T, Wu W and Wu Y: The effects of ginsenoside Rb1 on endothelial damage and ghrelin expression induced by hyperhomocysteine. J Vasc Surg. 53:156–164. 2011.PubMed/NCBI View Article : Google Scholar
13	Zheng X, Wang S, Zou X, Jing Y, Yang R, Li S and Wang F: Ginsenoside Rb1 improves cardiac function and remodeling in heart failure. Exp Anim. 66:217–228. 2017.PubMed/NCBI View Article : Google Scholar
14	Valencia-Nuñez DM, Kreutler W, Moya-Gonzalez J, Alados-Arboledas P, Muñoz-Carvajal I, Carmona A, Ramirez-Chamond R and Carracedo-Añon J: Endothelial vascular markers in coronary surgery. Heart Vessels. 32:1390–1399. 2017.PubMed/NCBI View Article : Google Scholar
15	Santilli F, Marchisio M, Lanuti P, Boccatonda A, Miscia S and Davi G: Microparticles as new markers of cardiovascular risk in diabetes and beyond. Thromb Haemost. 116:220–234. 2016.PubMed/NCBI View Article : Google Scholar
16	Sierko E, Sokół M and Wojtukiewicz MZ: Endothelial microparticles (EMP) in physiology and pathology. Postepy Hig Med Dosw (Online). 69:925–932. 2015.PubMed/NCBI View Article : Google Scholar : (In Polish).
17	Wu Q, Chen H, Fang J, Xie W, Hong M and Xia L: Elevated Fas/FasL system and endothelial cell microparticles are involved in endothelial damage in acute graft-versus-host disease: A clinical analysis. Leuk Res. 36:275–280. 2012.PubMed/NCBI View Article : Google Scholar
18	Campello E, Spiezia L, Radu CM, Bulato C, Gavasso S, Tormene D, Woodhams B, Dalla Valle F and Simioni P: Circulating microparticles and the risk of thrombosis in inherited deficiencies of antithrombin, protein C and protein S. Thromb Haemost. 115:81–88. 2016.PubMed/NCBI View Article : Google Scholar
19	Atehortúa L, Rojas M, Vásquez G, Muñoz-Vahos CH, Vanegas-García A, Posada-Duque RA and Castaño D: Endothelial activation and injury by microparticles in patients with systemic lupus erythematosus and rheumatoid arthritis. Arthritis Res Ther. 21(34)2019.PubMed/NCBI View Article : Google Scholar
20	Mobarrez F, Svenungsson E and Pisetsky DS: Microparticles as autoantigens in systemic lupus erythematosus. Eur J Clin Invest. 48(e13010)2018.PubMed/NCBI View Article : Google Scholar
21	Xia Q, Zhao Y, Lin G, Beland FA, Cai L and Fu PP: Pyrrolizidine alkaloid-protein adducts: Potential non-invasive biomarkers of pyrrolizidine alkaloid-induced liver toxicity and exposure. Chem Res Toxicol. 29:1282–1292. 2016.PubMed/NCBI View Article : Google Scholar
22	Stegelmeier BL, Colegate SM and Brown AW: Dehydropyrrolizidine alkaloid toxicity, cytotoxicity, and carcinogenicity. Toxins (Basel). 8(356)2016.PubMed/NCBI View Article : Google Scholar
23	Tamariz J, Burgueno-Tapia E, Vázquez MA and Delgado F: Pyrrolizidine Alkaloids. Alkaloids Chem Biol. 80:1–314. 2018.PubMed/NCBI View Article : Google Scholar
24	Kleiner DE: The histopathological evaluation of drug-induced liver injury. Histopathology. 70:81–93. 2017.PubMed/NCBI View Article : Google Scholar
25	Fang J, Zhang G, Teng X, Zhang Z, Pan J, Shou Q and Chen M: Hematologic toxicity of Gynura segetum and effects on vascular endothelium in a rat model of hepatic veno-occlusive disease. Zhonghua Gan Zang Bing Za Zhi. 23:59–63. 2015.PubMed/NCBI View Article : Google Scholar : (In Chinese).
26	Wasinee K, Kunwadee P, Kittiphong P, Kovit P, Pornthip C and Saovaros S: Microparticles From β-thalassaemia/HbE patients induce endothelial cell dysfunction. Sci Rep. 8(13033)2018.PubMed/NCBI View Article : Google Scholar
27	The composition and daily variation of microparticles in whole blood in stable coronary artery disease. J Physiol Pharmacol. 69:6–9. 2018.
28	Christersson C, Lindahl B and Siegbahn A: The composition and daily variation of microparticles in whole blood in stable coronary artery disease. Scand J Clin Lab Invest. 76:25–32. 2016.PubMed/NCBI View Article : Google Scholar
29	Jia F, Mou L and Ge H: Protective effects of ginsenoside Rb1 on H₂O₂-induced oxidative injury in human endothelial cell line (EA. hy926) via miR-210. Int J Immunopathol Pharmacol. 33(1681103269)2019.PubMed/NCBI View Article : Google Scholar
30	Beumer TL, Roepers-Gajadien HL, Gademan IS, Lock TM, Kal HB and De Rooij DG: Apoptosis regulation in the testis: Involvement of Bcl-2 family members. Mol Reprod Dev. 56:353–359. 2000.PubMed/NCBI View Article : Google Scholar
31	Sansone R, Baaken M, Horn P, Schuler D, Westenfeld R, Amabile N, Kelm M and Heiss C: Release of endothelial microparticles in patients with arterial hypertension, hypertensive emergencies and catheter-related injury. Atherosclerosis. 273:67–74. 2018.PubMed/NCBI View Article : Google Scholar
32	Jenkins NT, Padilla J, Boyle LJ, Credeur DP, Laughlin MH and Fadel PJ: Disturbed blood flow acutely induces activation and apoptosis of the human vascular endothelium. Hypertension. 61:615–621. 2013.PubMed/NCBI View Article : Google Scholar
33	Kou Y, Zou L, Liu R, Zhao X, Wang Y, Zhang C, Dong Z, Kou J, Bi Y, Fu L and Shi J: Intravascular cells and circulating microparticles induce procoagulant activity via phosphatidylserine exposure in heart failure. J Thromb Thrombolysis. 48:187–194. 2019.PubMed/NCBI View Article : Google Scholar
34	Shustova ON, Antonova OA, Golubeva NV, Khaspekova SG, Yakushkin VV, Aksuk SA, Alchinova IB, Karganov MY and Mazurov AV: Differential procoagulant activity of microparticles derived from monocytes, granulocytes, platelets and endothelial cells: Impact of active tissue factor. Blood Coagul Fibrinolysis. 28:373–382. 2017.PubMed/NCBI View Article : Google Scholar
35	Geddings JE and Mackman N: Tumor-derived tissue factor-positive microparticles and venous thrombosis in cancer patients. Blood. 122:1873–1880. 2013.PubMed/NCBI View Article : Google Scholar
36	Cheng X, Qiu X, Liu Y, Yuan C and Yang X: Trimethylamine N-oxide promotes tissue factor expression and activity in vascular endothelial cells: A new link between trimethylamine N-oxide and atherosclerotic thrombosis. Thromb Res. 177:110–116. 2019.PubMed/NCBI View Article : Google Scholar
37	Collier M, Akinmolayan A and Goodall AH: Comparison of tissue factor expression and activity in foetal and adult endothelial cells. Blood Coagul Fibrinolysis. 28:452–459. 2017.PubMed/NCBI View Article : Google Scholar