Cilostazol Induces eNOS and TM Expression via Activation with Sirtuin 1/Kruppel-like Factor 2 Pathway in Endothelial Cells

被引：12

作者：

Wu, Chih-Hsien ^{[1
,2
]}

Chiu, Yi-Lin ^{[1
]}

Hsieh, Chung-Yueh ^{[3
]}

Tsung, Guo-Shiang ^{[3
]}

Wu, Lian-Shan ^{[4
]}

Cheng, Cheng-Chung ^{[2
]}

Tsai, Tsung-Neng ^{[2
]}

机构：

[1] Natl Def Med Ctr, Dept Biochem, Taipei 114201, Taiwan

[2] Natl Def Med Ctr, Triserv Gen Hosp, Dept Internal Med, Div Cardiol, Taipei 114202, Taiwan

[3] Taoyuan Armed Forces Gen Hosp, Dept Internal Med, Div Cardiol, Taoyuan 325208, Taiwan

[4] Hualien Armed Forces Gen Hosp, Dept Internal Med, Div Cardiol, Xincheng 325208, Hualien County, Taiwan

来源：

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES | 2021年 / 22卷 / 19期

关键词：

cilostazol; endothelial cells; Kruppel-like factor 2; endothelial nitric oxide synthase; nitric oxide; thrombomodulin; KRUPPEL-LIKE FACTOR-2; NITRIC-OXIDE SYNTHASE; SHEAR-STRESS; GENE-EXPRESSION; PLATELET-AGGREGATION; KLF2; EXPRESSION; PROTEIN-KINASE; GROWTH-FACTOR; TRANSCRIPTION; AKT;

D O I：

10.3390/ijms221910287

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.</p>

引用

页数：12

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