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

Chih-Hsien Wu1,2, Yi-Lin Chiu1, Chung-Yueh Hsieh3

  • 1National Defense Medical Center, Department of Biochemistry, Taipei 114201, Taiwan.

International Journal of Molecular Sciences
|October 13, 2021
PubMed

Insights

Cilostazol enhances endothelial cell function by activating KLF2 and SIRT1, leading to increased nitric oxide production and reduced thrombosis risk. This study clarifies its antithrombotic mechanisms.

Area of Science:

  • Vascular Biology
  • Pharmacology

Background:

  • Cilostazol is known to reduce in-stent atherosclerosis and thrombosis.
  • The precise mechanisms underlying cilostazol's beneficial vascular effects remain unclear.

Purpose of the Study:

  • To investigate the antithrombotic mechanisms of cilostazol in endothelial cells.
  • To elucidate the role of KLF2, SIRT1, eNOS, and TM in cilostazol's effects.

Main Methods:

  • Human umbilical vein endothelial cells (HUVECs) were treated with varying concentrations of cilostazol.
  • Expression levels of KLF2, SIRT1, eNOS, and TM were analyzed.
  • Endothelial function markers including nitric oxide (NO) production were assessed.

Main Results:

  • Cilostazol significantly upregulated KLF2 expression and related endothelial functions.
  • SIRT1 activation by cilostazol mediated the observed effects.
  • Increased eNOS activation, NO production, and TM secretion were observed.

Conclusions:

  • Cilostazol activates KLF2 and SIRT1 pathways in endothelial cells.
  • These activations contribute to cilostazol's antithrombotic and vasculoprotective properties.
  • Findings support cilostazol's potential therapeutic role in preventing vascular thrombosis.
Keywords:
Krüppel-like factor 2cilostazolendothelial cellsendothelial nitric oxide synthasenitric oxidethrombomodulin

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