Induction of cardiovascular pathology in a novel model of low-grade chronic inflammation.
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.
Smith
Brenda J
BJ
Department of Nutritional Sciences, Oklahoma State University, Stillwater, OK 74078, USA. bjsmith@okstate.edu
Lightfoot
Stan A
SA
Lerner
Megan R
MR
Denson
Kent D
KD
Morgan
Daniel L
DL
Hanas
Jay S
JS
Bronze
Michael S
MS
Postier
Russell G
RG
Brackett
Daniel J
DJ
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
D004343:Drug Implants; D018836:Inflammation Mediators; D008070:Lipopolysaccharides