title: Atherosclerotic mice exhibit systemic inflammation in periadventitial and visceral adipose tissue, liver, and pancreatic islets.
abstract: OBJECTIVE
  Atherosclerosis is a chronic inflammatory disease of major conduit arteries. Similarly, obesity and type 2 diabetes mellitus are associated with accumulation of macrophages in visceral white adipose tissue and pancreatic islets. Our goal was to characterize systemic inflammation in atherosclerosis with hypercholesterolemia, but without obesity.
  
  
  RESULTS
  We compared 22-week-old apolipoprotein E knockout (ApoE(-/-)) with wild-type mice kept for 14 weeks on a high cholesterol (1.25%) diet (CD, n=8) and 8-week-old ApoE(-/-) with wild-type mice kept on a normal diet (ND, n=8). Hypercholesterolemic, atherosclerotic ApoE(-/-) mice on CD exhibited increased macrophages and T-cells in plaques and periadventitial adipose tissue that revealed elevated expression of MIP-1alpha, IL-1beta, IL-1 receptor, and IL-6. Mesenteric adipose tissue and pancreatic islets in ApoE(-/-) mice showed increased macrophages. Expression of IL-1beta was enhanced in mesenteric adipose tissue of ApoE(-/-) mice on CD. Furthermore, these mice exhibited steatohepatitis with macrophage and T-cell infiltrations as well as increased MIP-1alpha and IL-1 receptor expression. Blood glucose, insulin and total body weight did not differ between the groups.
  
  
  CONCLUSIONS
  In hypercholesterolemic lean ApoE(-/-) mice, inflammation extends beyond atherosclerotic plaques to the periadventitial and visceral adipose tissue, liver, and pancreatic islets without affecting glucose homeostasis.
authors.affiliation: Cardiovascular Research, Institute of Physiology, Zurich University and Cardiology, Cardiovascular Center, University Hospital Zurich, Zurich, Switzerland.
authors.forename: Christine
authors.initials: C
authors.lastname: Lohmann
authors.forename: Nicola
authors.initials: N
authors.lastname: Schäfer
authors.forename: Tobias
authors.initials: T
authors.lastname: von Lukowicz
authors.forename: M A
authors.initials: MA
authors.lastname: Sokrates Stein
authors.forename: Jan
authors.initials: J
authors.lastname: Borén
authors.forename: Sabine
authors.initials: S
authors.lastname: Rütti
authors.forename: Walter
authors.initials: W
authors.lastname: Wahli
authors.forename: Marc Y
authors.initials: MY
authors.lastname: Donath
authors.forename: Thomas F
authors.initials: TF
authors.lastname: Lüscher
authors.forename: Christian M
authors.initials: CM
authors.lastname: Matter
mesh_terms: D000818:Animals; D001057:Apolipoproteins E / Q000172:deficiency / Q000235:genetics; D050197:Atherosclerosis / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D001786:Blood Glucose / Q000378:metabolism; D001835:Body Weight; D003238:Connective Tissue / Q000276:immunology* / Q000473:pathology; D016207:Cytokines / Q000097:blood; D004195:Disease Models, Animal; D005234:Fatty Liver / Q000276:immunology / Q000473:pathology; D006937:Hypercholesterolemia / Q000150:complications* / Q000235:genetics / Q000276:immunology / Q000473:pathology; D007249:Inflammation / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D018836:Inflammation Mediators / Q000097:blood; D007328:Insulin / Q000097:blood; D050152:Intra-Abdominal Fat / Q000276:immunology* / Q000473:pathology; D007515:Islets of Langerhans / Q000276:immunology* / Q000473:pathology; D008099:Liver / Q000276:immunology* / Q000473:pathology; D008264:Macrophages / Q000276:immunology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: D001057:Apolipoproteins E; D001786:Blood Glucose; D016207:Cytokines; D018836:Inflammation Mediators; D007328:Insulin