Published online before print September 29, 2005, doi: 10.1161/01.ATV.0000188508.40052.35
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© 2005 American Heart Association, Inc.
Atherosclerosis and Lipoproteins |
Production of Chemokines by Perivascular Adipose Tissue
A Role in the Pathogenesis of Atherosclerosis?
From the Endocrine Unit, Department of Internal Medicine, University Hospital, Faculty of Medicine (E.H., C.E.J.-A., A.P., C.A.M.); Department of Cellular Physiology and Metabolism, Faculty of Medicine (E.H., C.E.J.-A., A.P., P.M., C.A.M.); Department of Pathology, Faculty of Medicine (J.-C.P.); Department of Cardiovascular Surgery, La Tour Hospital (V.V.); and the Division of Immunology and Allergy, Department of Internal Medicine, University Hospital, Faculty of Medicine (J.M.-D., C.C.), Geneva, Switzerland.
Correspondence to Dr Christoph A. Meier, Endocrine Unit, University Hospital Geneva, 24, rue Micheli-du-Crest, CH-1211 Geneva 14, Switzerland. E-mail Christoph.Meier{at}medecine.unige.ch
Objective— Obesity is associated with an increased risk for cardiovascular disease. Although it is known that white adipose tissue (WAT) produces numerous proinflammatory and proatherogenic cytokines and chemokines, it is unclear whether adipose-derived chemotactic signals affect the chronic inflammation in atherosclerosis.
Methods and Results— Histological examination showed that perivascular WAT (pWAT) is in close proximity to vascular walls, particularly at sites that have a tendency to develop atherosclerosis. In rodents, the amount of pWAT is markedly increased by a high-fat diet. At a functional level, supernatant from subcutaneous and pWAT strongly induced the chemotaxis of peripheral blood leukocytes. The migration of granulocytes and monocytes was mostly mediated by interleukin-8 and monocyte chemoattractant protein-1, respectively, whereas both chemokines contributed to the migration of activated T cells. Moreover, pWAT produces these chemokines, as shown by immunohistochemistry and by explant culture. The accumulation of macrophages and T cells at the interface between pWAT and the adventitia of human atherosclerotic aortas may reflect this prochemotactic activity of pWAT.
Conclusions— Human pWAT has chemotactic properties through the secretion of different chemokines, and we propose that pWAT might contribute to the progression of obesity-associated atherosclerosis.
Perivascular adipose tissue (pWAT) is found in close proximity of the vascular wall of aortas. This strategic location suggests an impact of pWAT on vascular wall function. Indeed, supernatant from human pWAT has a net chemotactic effect on blood leukocytes, which is mainly mediated via the secretion of chemokines.
Key Words: chemokines • perivascular adipose tissue • chemotaxis • obesity • inflammation
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