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Caveolin‐1 is a Negative Regulator of Adam17 in Adipose Tissue Vascular Endothelium
Author(s) -
Dou Huijuan,
RomeroLucas Maritza,
Bagi Zsolt
Publication year - 2015
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.29.1_supplement.634.9
Subject(s) - caveolin 1 , adipose tissue , tumor necrosis factor alpha , proinflammatory cytokine , medicine , endocrinology , endothelium , cytokine , adam10 , matrix metalloproteinase , metalloproteinase , immune system , inflammation , biology , chemistry , immunology , disintegrin
Aging is associated with increased level of proinflammatory cytokine, TNF. Pericardial adipose tissue (pFat) is one of the important sources of TNF, but very little is known how the release of TNF is regulated in pFat and whether this changes in aging. We tested the hypothesis that a disintegrin and metalloproteinase, ADAM17 (known as TNF converting enzyme or TACE) mediates an enhanced proteolytic shedding of membrane‐bound TNF from pFat in elderly patients. We obtained pFat from 47 consecutive patients (age between 40 and 80 yo) undergoing heart surgery. Immunohistochemistry and immune‐electron microscopy showed that within the pFat the vascular endothelium exhibits a prominent ADAM17 expression, with much less extent in adipocytes. In the superfusates of intact pFat vessels TNF release was significantly higher in older (>70 yo) then in younger (<70 yo) patients, which was inhibited by the ADAM17 inhibitor, TIMP‐3. Correspondingly, we found an age‐related increased ADAM17 activity in pFat vessels. We also found an age‐related decline in caveolin‐1 (Cav1) expression in pFat vessels and observed a reduced co‐localization between Cav1 and ADAM17 in older patients. In primarily cultured pFat endothelial cells genetic deletion of Cav1 increased ADAM17 activity. Thus, we propose that due to the age‐related deficit in Cav1‐mediated inhibition the activity of endothelial ADAM17, hence TNF release from pFAT is elevated in aging.