title: Rosuvastatin Inhibits Interleukin (IL)-8 and IL-6 Production in Human Coronary Artery Endothelial Cells Stimulated With Aggregatibacter actinomycetemcomitans Serotype b.
abstract: Rosuvastatin exhibits anti-inflammatory effects and reduces periodontal diseases and atherosclerosis; however, its role in regulating periodontopathogen-induced endothelial proinflammatory responses remains unclear. The purpose of this study is to determine whether rosuvastatin can reduce the proinflammatory response induced by Aggregatibacter actinomycetemcomitans (Aa) in human coronary artery endothelial cells (HCAECs).
  
  
  
  HCAECs were stimulated with purified Aa serotype b lipopolysaccharide (LPS) (Aa-LPS), heat-killed (HK) bacteria (Aa-HK), or live bacteria. Expression of Toll-like receptors and cellular adhesion molecules were evaluated by fluorometric enzyme-linked immunosorbent assay. Endothelial cell activation was evaluated by quantifying nuclear factor (NF)-kappa B-p65 and cytokine expression levels by quantitative polymerase chain reaction and flow cytometry. Effect of rosuvastatin in expression of the atheroprotective factor Krüppel-like factor 2 (KLF2) and cytokines were also studied using similar approaches.
  
  
  
  HCAECs showed increased interleukin (IL)-6, IL-8, intercellular adhesion molecule 1, and platelet endothelial cell adhesion molecule 1 expression when stimulated with Aa-LPS or Aa-HK. NF-κB-p65 activation was induced by all antigens. Aa-induced IL-6 and IL-8 production was inhibited by rosuvastatin, particularly at higher doses. Interestingly, reduced IL-6 and IL-8 levels were observed in HCAECs stimulated with Aa in the presence of higher concentrations of rosuvastatin. This anti-inflammatory effect correlated with a significant increase of rosuvastatin-induced KLF2.
  
  
  
  These results suggest Aa-induced proinflammatory endothelial responses are regulated by rosuvastatin in a mechanism that appears to involve KLF2 activation. Use of rosuvastatin to prevent cardiovascular disease may reduce risk of endothelial activation by bacterial antigens.
authors.affiliation: Unit of Basic Oral Investigation-UIBO, School of Dentistry, El Bosque University, Bogota, Colombia.
authors.forename: Diego F
authors.initials: DF
authors.lastname: Gualtero
authors.affiliation: Unit of Basic Oral Investigation-UIBO, School of Dentistry, El Bosque University, Bogota, Colombia.
authors.forename: Sergio M
authors.initials: SM
authors.lastname: Viafara-Garcia
authors.affiliation: Unit of Basic Oral Investigation-UIBO, School of Dentistry, El Bosque University, Bogota, Colombia.
authors.forename: Sandra J
authors.initials: SJ
authors.lastname: Morantes
authors.affiliation: Unit of Basic Oral Investigation-UIBO, School of Dentistry, El Bosque University, Bogota, Colombia.
authors.forename: Diana M
authors.initials: DM
authors.lastname: Buitrago
authors.affiliation: Center for Oral Health Research, College of Dentistry, University of Kentucky, Lexington, KY.
authors.forename: Octavio A
authors.initials: OA
authors.lastname: Gonzalez
authors.affiliation: Unit of Basic Oral Investigation-UIBO, School of Dentistry, El Bosque University, Bogota, Colombia.
authors.forename: Gloria I
authors.initials: GI
authors.lastname: Lafaurie
mesh_terms: D016976:Aggregatibacter actinomycetemcomitans / Q000472:pathogenicity*; D015415:Biomarkers / Q000378:metabolism; D003331:Coronary Vessels / Q000166:cytology*; D042783:Endothelial Cells / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism*; D016209:Interleukin-8 / Q000378:metabolism*; D008070:Lipopolysaccharides; D016328:NF-kappa B / Q000378:metabolism; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism; D016133:Polymerase Chain Reaction; D000068718:Rosuvastatin Calcium / Q000494:pharmacology*
chemical_list: D015415:Biomarkers; D015850:Interleukin-6; D016209:Interleukin-8; D008070:Lipopolysaccharides; D016328:NF-kappa B; D019408:Platelet Endothelial Cell Adhesion Molecule-1; C036757:lipopolysaccharide B; D018799:Intercellular Adhesion Molecule-1; D000068718:Rosuvastatin Calcium
keywords: Atherosclerosis; KLF2 proteins; immunity, innate; lipopolysaccharides; periodontitis