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Statins ameliorate cholesterol-induced inflammation and improve AQP2 expression by inhibiting NLRP3 activation in the

Yonglun Kong1,2, Weijing Feng1,3,4, Xiaoduo Zhao2

  • 1Department of Cardiology, The Eighth Affiliated Hospital, Sun Yat-sen University, Shenzhen 518033, China.

Theranostics
|September 15, 2020
PubMed

Insights

Statins may improve kidney water handling in chronic kidney disease by reducing cholesterol-induced inflammation and promoting aquaporin-2 (AQP2) expression, despite controversial effects on kidney function. This study investigated statin effects on renal AQP2 and NLRP3 inflammasome.

Area of Science:

  • Nephrology
  • Cardiovascular Medicine
  • Molecular Biology

Background:

  • Chronic kidney disease (CKD) is linked to dyslipidemia, with statins recommended for cardiovascular risk but controversial for kidney disease progression.
  • The impact of statins on renal water handling and kidney disease progression remains unclear.

Purpose of the Study:

  • To investigate statin treatment effects on renal water handling in patients and animal models with high-fat diet-induced dyslipidemia.
  • To examine the relationship between serum cholesterol, aquaporin-2 (AQP2), and the NLRP3 inflammasome in kidney disease.

Main Methods:

  • Retrospective analysis of patient kidney biopsy data to assess AQP2 and ASC protein expression.
  • In vivo studies using Nlrp3-deficient mice and 5/6 nephrectomized rats on a high-fat diet, treated with statins.
  • In vitro experiments to evaluate cholesterol and statin effects on NLRP3 inflammasome components and AQP2.

Main Results:

  • Serum cholesterol negatively correlated with estimated glomerular filtration rate (eGFR) and kidney AQP2 expression in patients; statins abolished this correlation without affecting eGFR.
  • High-fat diet decreased AQP2 and increased urine output in mice, an effect attenuated by Nlrp3 deficiency.
  • Atorvastatin decreased urine output and increased AQP2 in rats; in vitro, cholesterol upregulated NLRP3 components and decreased AQP2, effects prevented by statins via ASC speck degradation.

Conclusions:

  • Serum cholesterol negatively impacts kidney AQP2 expression in CKD patients.
  • Statins ameliorate cholesterol-induced renal inflammation by promoting ASC speck degradation and improving aquaporin expression in high-fat diet animal models.

Keywords:
AQP2ASCIL-1βcholesterolstatins

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