Atherosclerotic mice exhibit systemic inflammation in periadventitial and visceral adipose tissue, liver, and pancreatic islets

• Published in: Atherosclerosis 2009-12, Vol.207 (2), p.360-367
• Main Authors: Lohmann, Christine, Schäfer, Nicola, von Lukowicz, Tobias, Sokrates Stein, M.A, Borén, Jan, Rütti, Sabine, Wahli, Walter, Donath, Marc Y, Lüscher, Thomas F, Matter, Christian M
• Format: Article
• Language: English
• Subjects: Adipose tissue; Animals; Apolipoproteins E - deficiency; Apolipoproteins E - genetics; Atherosclerosis; Atherosclerosis (general aspects, experimental research); Atherosclerosis - genetics; Atherosclerosis - immunology; Atherosclerosis - pathology; Biological and medical sciences; Blood and lymphatic vessels; Blood Glucose - metabolism; Body Weight; Cardiology. Vascular system; Cardiovascular; Connective Tissue - immunology; Connective Tissue - pathology; Cytokines - blood; Disease Models, Animal; Fatty Liver - immunology; Fatty Liver - pathology; Hypercholesterolemia; Hypercholesterolemia - complications; Hypercholesterolemia - genetics; Hypercholesterolemia - immunology; Hypercholesterolemia - pathology; Immunomodulators; Inflammation - genetics; Inflammation - immunology; Inflammation - pathology; Inflammation Mediators - blood; Insulin - blood; Intra-Abdominal Fat - immunology; Intra-Abdominal Fat - pathology; Islets of Langerhans - immunology; Islets of Langerhans - pathology; Liver - immunology; Liver - pathology; Macrophages; Macrophages - immunology; Male; MEDICAL AND HEALTH SCIENCES; Medical sciences; MEDICIN OCH HÄLSOVETENSKAP; Mice; Mice, Inbred C57BL; Mice, Knockout; Pancreatic islets; Pharmacology. Drug treatments; T-Lymphocytes - immunology
• ISSN: 0021-9150; 1879-1484; 1879-1484
• DOI: 10.1016/j.atherosclerosis.2009.05.004

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. Methods and 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-1α , IL-1β , IL-1 receptor , and IL-6 . Mesenteric adipose tissue and pancreatic islets in ApoE−/− mice showed increased macrophages. Expression of IL-1β 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-1α 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.