Production of chemokines by perivascular adipose tissue: a role in the pathogenesis of atherosclerosis?
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.


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.
Henrichot
Elvire
E
Department of Internal Medicine, University Hospital, Faculty of Medicine, Geneva, Switzerland.
Juge-Aubry
Cristiana E
CE
Pernin
Agnès
A
Pache
Jean-Claude
JC
Velebit
Valdimir
V
Dayer
Jean-Michel
JM
Meda
Paolo
P
Chizzolini
Carlo
C
Meier
Christoph A
CA
D000273:Adipose Tissue / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D000818:Animals; D001011:Aorta / Q000473:pathology; D050197:Atherosclerosis / Q000276:immunology* / Q000378:metabolism; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000378:metabolism*; D002634:Chemotaxis, Leukocyte / Q000276:immunology; D004036:Diet, Atherogenic; D004041:Dietary Fats / Q000494:pharmacology; D006098:Granulocytes / Q000166:cytology; D006801:Humans; D016209:Interleukin-8 / Q000378:metabolism*; D009000:Monocytes / Q000166:cytology; D009765:Obesity / Q000276:immunology / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
C111835:CCL2 protein, human; D018932:Chemokine CCL2; D004041:Dietary Fats; D016209:Interleukin-8