Tumor necrosis factor-alpha does not mediate diabetes-induced vascular inflammation in mice.

Summary, in English

OBJECTIVE: Vascular inflammation is a key feature of both micro- and macrovascular complications in diabetes. Several lines of evidence have implicated the cytokine tumor necrosis factor (TNF) alpha as an important mediator of inflammation in diabetes. In the present study we evaluated the role of TNF alpha in streptozotocin (STZ)-induced diabetes on vascular inflammation in C57BL/6 wild-type and apoE-/- mice. METHODS AND RESULTS: Diabetes increased the expression of vascular cell adhesion molecule (VCAM)-1 in cerebral arteries 150 m in diameter as well as the macrophage accumulation in aortic root atherosclerotic plaques in apoE-/- mice. A more pronounced vascular inflammatory response was observed in diabetic TNF alpha-deficient apoE-/- mice. These mice were also characterized by increased accumulation of IgG and IgM autoantibodies in atherosclerotic lesions. Diabetes also increased VCAM-1 expression and plaque formation in apoE-competent TNF alpha -/- mice, whereas no such effects were observed in C57BL/6 wild-type mice. CONCLUSIONS: The present findings suggest that TNF alpha does not mediate diabetic-induced vascular inflammation in mice and reveal an unexpected protective role for TNF alpha. These effects are partly attributable to a direct antiinflammatory role of TNF alpha, but may also reflect a defective development of the immune system in these mice.

• Författare: Jenny Öhman; Gunilla Nordin Fredrikson; Lisa Berglund; Carin Gustavsson; Eva Bengtsson; Maj-Lis Smith; Carl-David Agardh; Elisabet Agardh; Stefan Jovinge; Maria Gomez; Jan Nilsson
• Avdelning/ar: Kardiovaskulär forskning - immunitet och ateroskleros; Kärlfysiologi; Institutionen för kliniska vetenskaper, Malmö; Stamcellscentrum (SCC)
• Publiceringsår: 2009
• Språk: Engelska
• Sidor: 1465-1470
• Publikation/Tidskrift/Serie: Arteriosclerosis, Thrombosis and Vascular Biology
• Volym: 29
• Issue: 10
• Länkar: http://www.ncbi.nlm.nih.gov/pubmed/19755528?dopt=Abstract; http://dx.doi.org/10.1161/ATVBAHA.109.193862
• Dokumenttyp: Artikel i tidskrift
• Förlag: Lippincott Williams & Wilkins
• Ämne: Cardiac and Cardiovascular Systems
• Nyckelord: Lipoproteins; Inflammation: etiology; Diabetic Angiopathies: etiology; Experimental: complications; Diabetes Mellitus; Cerebral Arteries: chemistry; Blood Glucose: analysis; Autoantibodies: analysis; Apolipoproteins E: physiology; Atherosclerosis: etiology; Vascular Cell Adhesion Molecule-1: blood; LDL: immunology; Tumor Necrosis Factor-alpha: physiology
• Status: Published
• Forskningsgrupp: Cardiovascular Research - Immunity and Atherosclerosis; Vascular Physiology
• ISBN/ISSN/Övrigt: ISSN: 1524-4636