title: Rosuvastatin can block pro-inflammatory actions of transgenic human C-reactive protein without reducing its circulating levels.
abstract: OBJECTIVE
  Statins have antiinflammatory effects and are known to decrease risk of 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.
  
  
  RESULTS
  We studied the antiinflammatory effects of rosuvastatin in spontaneously hypertensive rats (SHR) transgenically expressing human CRP (CRP-transgenic SHR) and in nontransgenic SHR lacking human CRP (nontransgenic 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 TNFα without decreasing circulating levels of human CRP. In contrast, in the nontransgenic strain lacking human CRP, rosuvastatin treatment had little or no effect on IL6 and TNFα 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 nontransgenic strain.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Institute of Physiology, Academy of Sciences of the Czech Republic, Prague, Czech Republic.
authors.forename: Jan
authors.initials: J
authors.lastname: Šilhavý
authors.forename: Václav
authors.initials: V
authors.lastname: Zídek
authors.forename: Vladimír
authors.initials: V
authors.lastname: Landa
authors.forename: Miroslava
authors.initials: M
authors.lastname: Šimáková
authors.forename: Petr
authors.initials: P
authors.lastname: Mlejnek
authors.forename: Vojtěch
authors.initials: V
authors.lastname: Škop
authors.forename: Olena
authors.initials: O
authors.lastname: Oliyarnyk
authors.forename: Ludmila
authors.initials: L
authors.lastname: Kazdová
authors.forename: Massimiliano
authors.initials: M
authors.lastname: Mancini
authors.forename: Kathrin
authors.initials: K
authors.lastname: Saar
authors.forename: Herbert
authors.initials: H
authors.lastname: Schulz
authors.forename: Norbert
authors.initials: N
authors.lastname: Hübner
authors.forename: Theodore W
authors.initials: TW
authors.lastname: Kurtz
authors.forename: Michal
authors.initials: M
authors.lastname: Pravenec
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D002097:C-Reactive Protein / Q000235:genetics / Q000378:metabolism*; D004195:Disease Models, Animal; D005464:Fluorobenzenes / Q000494:pharmacology*; D005786:Gene Expression Regulation; D006801:Humans; D007249:Inflammation / Q000097:blood / Q000235:genetics / Q000276:immunology / Q000517:prevention & control*; D018836:Inflammation Mediators / Q000097:blood*; D015850:Interleukin-6 / Q000097:blood; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D011743:Pyrimidines / Q000494:pharmacology*; D051381:Rats; D011918:Rats, Inbred SHR; D055647:Rats, Transgenic; D000068718:Rosuvastatin Calcium; D013449:Sulfonamides / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
chemical_list: D000893:Anti-Inflammatory Agents; D005464:Fluorobenzenes; D018836:Inflammation Mediators; D015850:Interleukin-6; D011743:Pyrimidines; D013449:Sulfonamides; D014409:Tumor Necrosis Factor-alpha; D000068718:Rosuvastatin Calcium; D002097:C-Reactive Protein
keywords: C-reactive protein; cardiac inflammation; rosuvastatin; spontaneously hypertensive rat; transgenic