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J. Chin. Med."],"published-print":{"date-parts":[[2020,1]]},"abstract":"<jats:p> The effects of thrombo-prevention, such as antiplatelet and anticoagulant activity, have been reported with the usage of Ginkgo biloba extract (GbE); however, the detailed mechanism has not yet been fully investigated, especially the role of Kr\u00fcppel-like factor 2 (KLF2). This study aimed to investigate whether GbE can activate KLF2 and then induce thrombomodulin (TM) and tissue-type plasminogen activator (t-PA) secretion to enhance the effects of thrombo-prevention. Different concentrations of GbE were incubated with human umbilical vein endothelial cells (HUVECs) to evaluate its effect on endothelial cells. We found that KLF2 expression is correlated to the risk of atherosclerosis and venous thromboembolism in clinical practice. In the HUVEC cell model, GbE stimulated the expression of KLF2 in a dose-dependent manner. Moreover, TM and t-PA secretion increased when the cells were cultured with GbE.\u00a0Both the expressions and activities of TM and t-PA in the GbE-treated cells declined after KLF2 was blocked by shKLF2. In sum, with GbE treatment, KLF2 expression in human endothelial cells was significantly activated, which in turn induced an increase in the protein expression and activity of TM and t-PA.\u00a0After shRNA inhibited the KLF2 expression, GbE stopped inducing the expression and activity of TM and t-PA.\u00a0These findings suggest that GbE exerts an antithrombotic effect on endothelial cells by increasing the TM expression and t-PA secretion; further, KLF2 is a key factor in this mechanism. <\/jats:p>","DOI":"10.1142\/s0192415x20500184","type":"journal-article","created":{"date-parts":[[2020,2,28]],"date-time":"2020-02-28T16:16:17Z","timestamp":1582906577000},"page":"357-372","source":"Crossref","is-referenced-by-count":13,"title":["<i>Ginkgo biloba<\/i> Induces Thrombomodulin Expression and Tissue-Type Plasminogen Activator Secretion via the Activation of Kr\u00fcppel-Like Factor 2 within Endothelial Cells"],"prefix":"10.1142","volume":"48","author":[{"given":"Yi-Lin","family":"Chiu","sequence":"first","affiliation":[{"name":"Department of Biochemistry, National Defense Medical Center, Taipei 114, Taiwan, R.O.C."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei-Che","family":"Tsai","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei 114, Taiwan, R.O.C."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chih-Hsien","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, National Defense Medical Center, Taipei 114, Taiwan, R.O.C."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chun-Hsien","family":"Wu","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei 114, Taiwan, R.O.C."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cheng-Chung","family":"Cheng","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, National Defense Medical Center, Taipei 114, Taiwan, R.O.C."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei-Shing","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, National Defense Medical Center, Taipei 114, Taiwan, R.O.C."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tsung-Neng","family":"Tsai","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, National Defense Medical Center, Taipei 114, Taiwan, R.O.C."},{"name":"Division of Cardiology, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei 114, Taiwan, R.O.C."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lian-Shan","family":"Wu","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Department of Internal Medicine, Hualien Armed Forces General Hospital, Hualien County 971, Taiwan, R.O.C."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"219","published-online":{"date-parts":[[2020,2,28]]},"reference":[{"key":"S0192415X20500184BIB001","doi-asserted-by":"publisher","DOI":"10.1111\/j.1538-7836.2006.02138.x"},{"key":"S0192415X20500184BIB002","doi-asserted-by":"publisher","DOI":"10.1055\/s-2003-40454"},{"key":"S0192415X20500184BIB003","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.15.11.5957"},{"key":"S0192415X20500184BIB004","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.0000267856.00713.0a"},{"key":"S0192415X20500184BIB005","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM200103083441001"},{"key":"S0192415X20500184BIB006","doi-asserted-by":"publisher","DOI":"10.1002\/mnfr.200700098"},{"key":"S0192415X20500184BIB007","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0054891"},{"key":"S0192415X20500184BIB008","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(00)02225-X"},{"key":"S0192415X20500184BIB009","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btm254"},{"key":"S0192415X20500184BIB010","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V75.2.329.329"},{"key":"S0192415X20500184BIB011","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/30.1.207"},{"key":"S0192415X20500184BIB012","doi-asserted-by":"publisher","DOI":"10.1378\/chest.124.3_suppl.26S"},{"key":"S0192415X20500184BIB013","doi-asserted-by":"publisher","DOI":"10.2174\/1568016053544336"},{"key":"S0192415X20500184BIB014","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2009-05-219485"},{"key":"S0192415X20500184BIB015","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.109.191957"},{"key":"S0192415X20500184BIB016","doi-asserted-by":"publisher","DOI":"10.2147\/TCRM.S75024"},{"key":"S0192415X20500184BIB017","first-page":"249","volume":"19","author":"Lan W.J.","year":"2006","journal-title":"Biomed. 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