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

• Published in: International journal of molecular sciences Vol. 22; no. 19; p. 10287
• Main Authors: Wu, Chih-Hsien, Chiu, Yi-Lin, Hsieh, Chung-Yueh, Tsung, Guo-Shiang, Wu, Lian-Shan, Cheng, Cheng-Chung, Tsai, Tsung-Neng
• Format: Journal Article
• Language: English
• Published: Basel MDPI AG 01.10.2021; MDPI
• Subjects: Arteriosclerosis; Atherosclerosis; Bioavailability; Blood clots; Blood platelets; Cardiovascular system; Cell adhesion & migration; Cell cycle; cilostazol; Drug dosages; Endothelial cells; endothelial nitric oxide synthase; Flow cytometry; Gene expression; Homeostasis; Implants; Kinases; Krueppel-like factor; Krüppel-like factor 2; Nitric oxide; Nitric-oxide synthase; Patients; Proteins; Shear stress; SIRT1 protein; Smooth muscle; Stents; thrombomodulin; Thrombosis; Transcription; Umbilical vein
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms221910287

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.