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Klotho Contributes to Pravastatin Effect on Suppressing IL-6 Production in Endothelial Cells

Weiwei Xia1, Aihua Zhang2, Zhanjun Jia2

  • 1Department of Clinical Laboratory, Nanjing Children's Hospital, Nanjing Medical University, Nanjing 210008, China; Jiangsu Key Laboratory of Pediatrics, Nanjing 210029, China; State Key Laboratory of Protein and Plant Gene Research, College of Life Science, Peking University, Beijing 100871, China.

Mediators of Inflammation
|April 2, 2016
PubMed

Insights

Pravastatin, a statin, reduces interleukin-6 (IL-6) by increasing klotho in endothelial cells. This suggests a new mechanism for statin benefits in vascular diseases, particularly atherosclerosis.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Cardiovascular Research

Background:

  • Statins and klotho offer vascular benefits.
  • Interleukin-6 (IL-6) indicates atherosclerotic plaque stability and contributes to atherosclerosis.
  • The interplay between statins, klotho, and IL-6 in inflammation is unclear.

Purpose of the Study:

  • To investigate the effect of pravastatin on klotho and IL-6 expression in endothelial cells under inflammatory conditions.
  • To elucidate the role of klotho in mediating the effects of statins on IL-6 production.

Main Methods:

  • Primary human umbilical vein endothelial cells (HUVECs) were used for in vitro studies.
  • Quantitative reverse transcription polymerase chain reaction (qRT-PCR) and enzyme-linked immunosorbent assay (ELISA) were employed.
  • Klotho overexpression and TNF-α stimulation were utilized to assess IL-6 modulation.
  • Peripheral blood mononuclear cells (PBMCs) from atherosclerosis patients were analyzed.

Main Results:

  • Pravastatin dose-dependently increased klotho expression and suppressed IL-6 in HUVECs.
  • Pravastatin partially blunted TNF-α-induced IL-6 production.
  • Klotho overexpression significantly attenuated TNF-α-induced IL-6 production.
  • Atherosclerosis patients showed reduced klotho mRNA expression in PBMCs.

Conclusions:

  • Pravastatin suppresses IL-6 production by promoting klotho expression in endothelial cells during inflammation.
  • This mechanism may contribute to the vascular benefits of statins in atherosclerosis.

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