Atherosclerotic mice exhibit systemic inflammation in periadventitial and visceral adipose tissue, liver, and pancreatic islets.
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.
Lohmann
Christine
C
Cardiovascular Research, Institute of Physiology, Zurich University and Cardiology, Cardiovascular Center, University Hospital Zurich, Zurich, Switzerland.
Schäfer
Nicola
N
von Lukowicz
Tobias
T
Sokrates Stein
M A
MA
Borén
Jan
J
Rütti
Sabine
S
Wahli
Walter
W
Donath
Marc Y
MY
Lüscher
Thomas F
TF
Matter
Christian M
CM
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
D001057:Apolipoproteins E; D001786:Blood Glucose; D016207:Cytokines; D018836:Inflammation Mediators; D007328:Insulin