title: Induction of cardiovascular pathology in a novel model of low-grade chronic inflammation.
abstract: OBJECTIVE
  Epidemiological and clinical evidence indicate that inflammatory processes play a pivotal role in a number of conditions associated with aging, including osteoporosis and cardiovascular diseases. The purpose of this study was to evaluate cardiovascular pathology and select inflammatory mediators of interest in a model of low-grade inflammation-induced osteopenia.
  
  
  METHODS
  Slow-release pellets were subcutaneously implanted in male rats to deliver 0, 3.3, or 33.3 microg of lipopolysaccharide (LPS)/day for 90 days. Tail blood was collected at 1, 2, and 3 months for differential white cell counts, and at the end of the study, hearts were harvested for histological and immunohistochemical evaluation.
  
  
  RESULTS
  The low-grade inflammatory response was characterized by elevated peripheral blood neutrophils and monocytes. Histological examination of heart cross sections revealed increased fibrous tissue, infiltration of lymphocytes, accumulation of mast cells, and roughened intimal borders within the arteries and arterioles, consistent with vascular disease. Inflammatory mediators (cyclooxygenase-2, tumor necrosis factor-alpha, and interleukin-1 beta) were up-regulated, and increased expression of platelet endothelial cell adhesion molecule-1 and receptor activator for NF-kappaB ligand was localized to the microvasculature endothelium.
  
  
  CONCLUSIONS
  These findings suggest that inflammation induced by chronic exposure to LPS produces cardiovascular pathology in the smaller intramural arteries and arterioles and support the utility of this model for further mechanistic and therapeutic studies focused on the role of chronic inflammation in cardiovascular disease.
authors.affiliation: Department of Nutritional Sciences, Oklahoma State University, Stillwater, OK 74078, USA. bjsmith@okstate.edu
authors.forename: Brenda J
authors.initials: BJ
authors.lastname: Smith
authors.forename: Stan A
authors.initials: SA
authors.lastname: Lightfoot
authors.forename: Megan R
authors.initials: MR
authors.lastname: Lerner
authors.forename: Kent D
authors.initials: KD
authors.lastname: Denson
authors.forename: Daniel L
authors.initials: DL
authors.lastname: Morgan
authors.forename: Jay S
authors.initials: JS
authors.lastname: Hanas
authors.forename: Michael S
authors.initials: MS
authors.lastname: Bronze
authors.forename: Russell G
authors.initials: RG
authors.lastname: Postier
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Brackett
mesh_terms: D000818:Animals; D001160:Arterioles / Q000378:metabolism / Q000473:pathology; D001851:Bone Diseases, Metabolic / Q000139:chemically induced / Q000276:immunology*; D002318:Cardiovascular Diseases / Q000139:chemically induced / Q000276:immunology* / Q000473:pathology*; D002467:Cell Nucleus / Q000378:metabolism / Q000473:pathology; D002908:Chronic Disease; D004195:Disease Models, Animal; D018450:Disease Progression; D004343:Drug Implants; D007249:Inflammation / Q000139:chemically induced / Q000276:immunology* / Q000473:pathology*; D018836:Inflammation Mediators / Q000378:metabolism; D007958:Leukocyte Count; D008070:Lipopolysaccharides; D008297:Male; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D032383:Myocytes, Cardiac / Q000378:metabolism / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D004343:Drug Implants; D018836:Inflammation Mediators; D008070:Lipopolysaccharides