Cilostazol Induces eNOS and TM Expression via Activation with Sirtuin 1/Krüppel-like Factor 2 Pathway in Endothelial Cells
Cilostazol was suggested to be beneficial to retard in-stent atherosclerosis and prevent stent thrombosis. However, the mechanisms responsible for the beneficial effects of cilostazol are not fully understood. In this study, we attempted to verify the mechanism of the antithrombotic effect of cilost...
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MDPI AG
2021-09-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/22/19/10287 |
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| author | Chih-Hsien Wu Yi-Lin Chiu Chung-Yueh Hsieh Guo-Shiang Tsung Lian-Shan Wu Cheng-Chung Cheng Tsung-Neng Tsai |
| author_facet | Chih-Hsien Wu Yi-Lin Chiu Chung-Yueh Hsieh Guo-Shiang Tsung Lian-Shan Wu Cheng-Chung Cheng Tsung-Neng Tsai |
| author_sort | Chih-Hsien Wu |
| collection | DOAJ |
| description | Cilostazol was suggested to be beneficial to retard in-stent atherosclerosis and prevent stent thrombosis. However, the mechanisms responsible for the beneficial effects of cilostazol are not fully understood. In this study, we attempted to verify the mechanism of the antithrombotic effect of cilostazol. Human umbilical vein endothelial cells (HUVECs) were cultured with various concentrations of cilostazol to verify its impact on endothelial cells. KLF2, silent information regulator transcript-1 (SIRT1), endothelial nitric oxide synthase (eNOS), and endothelial thrombomodulin (TM) expression levels were examined. We found cilostazol significantly activated KLF2 expression and KLF2-related endothelial function, including eNOS activation, Nitric oxide (NO) production, and TM secretion. The activation was regulated by SIRT1, which was also stimulated by cilostazol. These findings suggest that cilostazol may be capable of an antithrombotic and vasculoprotective effect in endothelial cells. |
| first_indexed | 2024-03-10T06:59:38Z |
| format | Article |
| id | doaj.art-2c669082a9164cc2ae489f4f5271ed52 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T06:59:38Z |
| publishDate | 2021-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-2c669082a9164cc2ae489f4f5271ed522023-11-22T16:07:16ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-09-0122191028710.3390/ijms221910287Cilostazol Induces eNOS and TM Expression via Activation with Sirtuin 1/Krüppel-like Factor 2 Pathway in Endothelial CellsChih-Hsien Wu0Yi-Lin Chiu1Chung-Yueh Hsieh2Guo-Shiang Tsung3Lian-Shan Wu4Cheng-Chung Cheng5Tsung-Neng Tsai6National Defense Medical Center, Department of Biochemistry, Taipei 114201, TaiwanNational Defense Medical Center, Department of Biochemistry, Taipei 114201, TaiwanDepartment of Internal Medicine, Division of Cardiology, Taoyuan Armed Forces General Hospital, Taoyuan City 325208, TaiwanDepartment of Internal Medicine, Division of Cardiology, Taoyuan Armed Forces General Hospital, Taoyuan City 325208, TaiwanDepartment of Internal Medicine, Division of Cardiology, Hualien Armed Forces General Hospital, Hualien County 325208, TaiwanDepartment of Internal Medicine, Division of Cardiology, Tri-Service General Hospital, National Defense Medical Center, Taipei 114202, TaiwanDepartment of Internal Medicine, Division of Cardiology, Tri-Service General Hospital, National Defense Medical Center, Taipei 114202, TaiwanCilostazol was suggested to be beneficial to retard in-stent atherosclerosis and prevent stent thrombosis. However, the mechanisms responsible for the beneficial effects of cilostazol are not fully understood. In this study, we attempted to verify the mechanism of the antithrombotic effect of cilostazol. Human umbilical vein endothelial cells (HUVECs) were cultured with various concentrations of cilostazol to verify its impact on endothelial cells. KLF2, silent information regulator transcript-1 (SIRT1), endothelial nitric oxide synthase (eNOS), and endothelial thrombomodulin (TM) expression levels were examined. We found cilostazol significantly activated KLF2 expression and KLF2-related endothelial function, including eNOS activation, Nitric oxide (NO) production, and TM secretion. The activation was regulated by SIRT1, which was also stimulated by cilostazol. These findings suggest that cilostazol may be capable of an antithrombotic and vasculoprotective effect in endothelial cells.https://www.mdpi.com/1422-0067/22/19/10287cilostazolendothelial cellsKrüppel-like factor 2endothelial nitric oxide synthasenitric oxidethrombomodulin |
| spellingShingle | Chih-Hsien Wu Yi-Lin Chiu Chung-Yueh Hsieh Guo-Shiang Tsung Lian-Shan Wu Cheng-Chung Cheng Tsung-Neng Tsai Cilostazol Induces eNOS and TM Expression via Activation with Sirtuin 1/Krüppel-like Factor 2 Pathway in Endothelial Cells International Journal of Molecular Sciences cilostazol endothelial cells Krüppel-like factor 2 endothelial nitric oxide synthase nitric oxide thrombomodulin |
| title | Cilostazol Induces eNOS and TM Expression via Activation with Sirtuin 1/Krüppel-like Factor 2 Pathway in Endothelial Cells |
| title_full | Cilostazol Induces eNOS and TM Expression via Activation with Sirtuin 1/Krüppel-like Factor 2 Pathway in Endothelial Cells |
| title_fullStr | Cilostazol Induces eNOS and TM Expression via Activation with Sirtuin 1/Krüppel-like Factor 2 Pathway in Endothelial Cells |
| title_full_unstemmed | Cilostazol Induces eNOS and TM Expression via Activation with Sirtuin 1/Krüppel-like Factor 2 Pathway in Endothelial Cells |
| title_short | Cilostazol Induces eNOS and TM Expression via Activation with Sirtuin 1/Krüppel-like Factor 2 Pathway in Endothelial Cells |
| title_sort | cilostazol induces enos and tm expression via activation with sirtuin 1 kruppel like factor 2 pathway in endothelial cells |
| topic | cilostazol endothelial cells Krüppel-like factor 2 endothelial nitric oxide synthase nitric oxide thrombomodulin |
| url | https://www.mdpi.com/1422-0067/22/19/10287 |
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