title: Very low density lipoproteins derived from periodontitis patients facilitate macrophage activation via lipopolysaccharide function.
abstract: OBJECTIVE
  Periodontitis, a chronic oral infection caused mainly by gram-negative bacteria, induces endotoxemia and associates with the risk for atherosclerosis. We investigated the effect of periodontal treatment on proatherogenic properties of very low density lipoproteins (VLDL).
  
  
  METHODS
  VLDL were isolated from 30 systemically healthy periodontitis patients before (pre-treatment) and 3 months after treatment (post-treatment). The mass compositions were analyzed, and VLDL-induced changes in cellular cholesterol content and expression of selected genes of human THP-1 macrophages were measured.
  
  
  RESULTS
  Periodontal treatment decreased the local inflammation in the periodontium, but did not have a significant effect on C-reactive protein (CRP) levels, VLDL composition, or VLDL potential to induce cholesterol uptake or gene expression by the macrophages. Incubation of macrophages in the presence of VLDL resulted in more than twofold increase in their cellular cholesterol content. Uptake of VLDL with ensuing macrophage cholesterol accumulation correlated positively with VLDL-associated lipopolysaccharide (LPS) activity (r=0.436, P=.016) and apolipoprotein E content (r=0.374, P=.046). Pre-treatment VLDL derived from the patients with high CRP levels displayed higher LPS activity than that of VLDL derived from patients with low CRP (above vs. below median, P=.007). In addition, pre-treatment VLDL isolated from patients with high systemic inflammation induced higher relative mRNA expression of CD14, TNF-α, MCP-1, and IL-6 in the macrophages.
  
  
  CONCLUSIONS
  Inflammation and endotoxemia induced by severe periodontitis may increase VLDL-dependent macrophage activation and cellular cholesterol accumulation, and thereby atherogenesis.
authors.affiliation: Institute of Dentistry, University of Helsinki, Helsinki, Finland. elisa.kallio@helsinki.fi
authors.forename: K A Elisa
authors.initials: KA
authors.lastname: Kallio
authors.forename: Kati
authors.initials: K
authors.lastname: Hyvärinen
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: D000328:Adult; D016022:Case-Control Studies; D002478:Cells, Cultured; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D019446:Endotoxemia / Q000097:blood / Q000235:genetics / Q000276:immunology / Q000628:therapy; D005260:Female; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology* / Q000502:physiology; D008079:Lipoproteins, VLDL / Q000097:blood* / Q000494:pharmacology*; D008262:Macrophage Activation / Q000187:drug effects* / Q000235:genetics; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism / Q000473:pathology / Q000502:physiology; D008297:Male; D008875:Middle Aged; D010518:Periodontitis / Q000097:blood* / Q000276:immunology / Q000473:pathology / Q000628:therapy
chemical_list: D016207:Cytokines; D018836:Inflammation Mediators; D008070:Lipopolysaccharides; D008079:Lipoproteins, VLDL