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Cellular and Molecular Life Sciences

, Volume 76, Issue 19, pp 3891–3898 | Cite as

The effect and molecular mechanism of statins on the expression of human anti-coagulation genes

  • Sheng-Nan Chang
  • Cho-Kai Wu
  • Ling-Ping Lai
  • Fu-Tien Chiang
  • Juey-Jen Hwang
  • Chia-Ti TsaiEmail author
Original Article
  • 207 Downloads

Abstract

Statins are potent lipid-lowering drugs. Large prospective clinical trials have shown the anti-thrombotic effect of statins, e.g., preventing deep vein thrombosis. However, the mechanism underlying the beneficial effect of statins in reducing thrombus formation remains to be established. We, thus, conduct this study to investigate the potential molecular mechanisms. The cultured human hepatoma cells (HepG2) were used as the in vitro model. The human protein C gene promoter was cloned into the luciferase reporter to study the transcriptional regulation of human protein C gene. Wistar rats fed with simvastatin (5 mg/kg day) were used as the in vivo model. We found that simvastatin increased the expression of protein C in hepatocytes (361 ± 64% and 313 ± 59% after 2 h and 6 h of stimulation, respectively, both p < 0.01). In the animal study, the serum protein C levels were increased in the simvastatin-treated group (7 ± 2.2 unit/ml vs 23.4 ± 19.3 unit/ml and 23.4 ± 18.2 unit/ml and 1 and 2 weeks of treatment, respectively, both p < 0.05). Regarding the possible molecular mechanism, we found that the level of hepatocyte nuclear factor 1α (HNF1α) was also increased in both the in vivo and in vitro models. We found that the protein C promoter activity was increased by simvastatin, and this effect was inhibited by HNF1α knockdown and constitutively active Rac1. Therefore, stains may modulate protein C expression through small GTPase Rac 1 and HNF1α.

Keywords

Inhibition of 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase Protein C Rac1 HNF 1α Anti-coagulation Gene 

Notes

Funding

This work was supported by the Ministry of Science and Technology, Taiwan [107-2314-B-002-256].

Compliance with ethical standards

Conflict of interest

All authors have no conflict of interest to declare.

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Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  • Sheng-Nan Chang
    • 1
    • 2
    • 3
  • Cho-Kai Wu
    • 2
  • Ling-Ping Lai
    • 2
  • Fu-Tien Chiang
    • 2
    • 4
  • Juey-Jen Hwang
    • 1
    • 2
  • Chia-Ti Tsai
    • 1
    • 2
    • 3
    Email author
  1. 1.Division of Cardiology, Department of Internal MedicineNational Taiwan University HospitalYun-LinTaiwan
  2. 2.Division of Cardiology, Department of Internal MedicineNational Taiwan University College of Medicine and HospitalTaipeiTaiwan
  3. 3.College of Medicine, Graduate Institute of Clinical MedicineNational Taiwan UniversityTaipeiTaiwan
  4. 4.Division of Cardiology, Department of Internal MedicineFu Jen Catholic University HospitalTaipeiTaiwan

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