title: The effect of proatherogenic microbes on macrophage cholesterol homeostasis in apoE-deficient mice.
abstract: BACKGROUND
  Pathogens such as Aggregatibacter actinomycetemcomitans (Aa) and Chlamydia pneumoniae (Cpn) associate with an increased risk for cardiovascular diseases by inducing inflammation. We hypothesized that the pathogens affect the vascular wall by disturbing cholesterol homeostasis and endothelial function.
  
  
  METHODS
  Aa- and Cpn-infections were induced in apoE-deficient mice by intravenous and intranasal applications, respectively. Cholesterol efflux from mouse peritoneal macrophages to apo(lipoprotein)A-I was assessed. The efflux capacity of mouse sera as acceptors of cholesterol from RAW264.7-macrophages was determined. Additionally, endothelial function was studied by following the relaxation capacity of rat mesenteric arteries after incubation in the conditioned culture media of the peritoneal macrophages isolated from the mice.
  
  
  RESULTS
  Infection increased serum phospholipid transfer protein (PLTP) and lipopolysaccharide (LPS) activity, as well as serum amyloid A (SAA) and TNF-α concentrations. Peritoneal macrophages of mice with Aa-infection showed increased cholesterol uptake and reduced cholesterol efflux. Sera of Cpn and Cpn + Aa-infected mice had reduced cholesterol efflux capacity from RAW264.7-macrophages. Conditioned macrophage medium from mice with chronic C. pneumoniae infection induced endothelial dysfunction. Additionally, concentrations of serum adhesion molecules, intercellular adhesion molecule (ICAM) and vascular cell adhesion molecule (VCAM) in Cpn-groups and E-selectin in Cpn + Aa-group, were elevated. The serum markers of endothelial function correlated positively with SAA.
  
  
  CONCLUSIONS
  Aa- and Cpn-infections may generate proatherogenic changes in the vascular wall by affecting the macrophage cholesterol homeostasis and endothelial function.
authors.affiliation: Institute of Dentistry, University of Helsinki, FI-00014 Helsinki, Finland.
authors.forename: Anita M
authors.initials: AM
authors.lastname: Tuomainen
authors.forename: Kati
authors.initials: K
authors.lastname: Hyvärinen
authors.forename: Pauliina I
authors.initials: PI
authors.lastname: Ehlers
authors.forename: Eero
authors.initials: E
authors.lastname: Mervaala
authors.forename: Maija
authors.initials: M
authors.lastname: Leinonen
authors.forename: Pekka
authors.initials: P
authors.lastname: Saikku
authors.forename: Petri T
authors.initials: PT
authors.lastname: Kovanen
authors.forename: Matti
authors.initials: M
authors.lastname: Jauhiainen
authors.forename: Pirkko J
authors.initials: PJ
authors.lastname: Pussinen
mesh_terms: D000818:Animals; D001057:Apolipoproteins E / Q000172:deficiency*; D023521:Chlamydophila Infections / Q000382:microbiology / Q000473:pathology; D016993:Chlamydophila pneumoniae / Q000472:pathogenicity*; D002784:Cholesterol / Q000378:metabolism*; D017077:Culture Media, Conditioned; D004195:Disease Models, Animal; D042783:Endothelial Cells / Q000502:physiology; D006706:Homeostasis; D008070:Lipopolysaccharides / Q000097:blood; D008264:Macrophages / Q000378:metabolism* / Q000382:microbiology*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D015661:Pasteurellaceae / Q000472:pathogenicity*; D016871:Pasteurellaceae Infections / Q000382:microbiology / Q000473:pathology; D049294:Phospholipid Transfer Proteins / Q000097:blood; D051381:Rats; D044967:Serum / Q000737:chemistry; D000685:Serum Amyloid A Protein / Q000032:analysis; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
chemical_list: D001057:Apolipoproteins E; D017077:Culture Media, Conditioned; D008070:Lipopolysaccharides; D049294:Phospholipid Transfer Proteins; D000685:Serum Amyloid A Protein; D014409:Tumor Necrosis Factor-alpha; D002784:Cholesterol