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Rosuvastatin can block pro-inflammatory actions of transgenic human CRP without reducing its circulating levels

Authors

  • J. Šilhavý
  • V. Zídek
  • V. Landa
  • M. Šimáková
  • P. Mlejnek
  • V. Škop
  • O. Oliyarnyk
  • L. Kazdová
  • M. Mancini
  • K. Saar
  • H. Schulz
  • N. Hübner
  • T.W. Kurtz
  • M. Pravenec

Journal

  • Cardiovascular Therapeutics

Citation

  • Cardiovasc Ther 32 (2): 59-65

Abstract

  • AIMS: Statins have anti-inflammatory effects and are known to decrease risk for cardiovascular events and to reduce serum levels of C-reactive protein (CRP), a widely studied biomarker and potential mediator of inflammation and heart disease. However, it is unclear whether statins can block pro-inflammatory effects of human CRP independent of their ability to reduce serum levels of human CRP. Here we investigated whether rosuvastatin could block pro-inflammatory effects of human CRP without reducing circulating levels of human CRP. METHODS AND RESULTS: We studied the anti-inflammatory effects of rosuvastatin in spontaneously hypertensive rats (SHR) transgenically expressing human CRP (CRP-transgenic SHR) and in non-transgenic SHR lacking human CRP (non-transgenic SHR). The CRP-transgenic SHR is characterized by increased serum levels of human CRP and inflammation. In the CRP-transgenic strain, we found that rosuvastatin treatment decreased circulating levels of inflammatory response markers IL6 and TNFalpha without decreasing circulating levels of human CRP. In contrast, in the non-transgenic strain lacking human CRP, rosuvastatin treatment had little or no effect on IL6 and TNFalpha levels. Rosuvastatin also reduced cardiac inflammation and oxidative tissue damage, reduced epididymal fat mass, and improved adipose tissue lipolysis much more in the CRP-transgenic strain than in the non-transgenic strain. CONCLUSION: Rosuvastatin can protect against pro-inflammatory effects of human CRP in a manner that is not dependent on achieving a reduction in circulating levels of human CRP.


DOI

doi:10.1111/1755-5922.12061