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Diabetologia

Erschienen in:

01.03.2004 | Article

Adipocytes release a soluble form of VAP-1/SSAO by a metalloprotease-dependent process and in a regulated manner

verfasst von: A. Abella, S. García-Vicente, N. Viguerie, A. Ros-Baró, M. Camps, M. Palacín, A. Zorzano, L. Marti

Erschienen in: Diabetologia | Ausgabe 3/2004

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Abstract

Aims/hypothesis

Vascular adhesion protein-1 (VAP-1), which is identical to semicarbazide-sensitive amine oxidase (SSAO), is a dual-function membrane protein with adhesion properties and amine oxidase activity. A soluble form of VAP-1 is found in serum, where concentrations are enhanced in diabetes and obesity. In vitro, soluble VAP-1 enhances lymphocyte adhesion to endothelial cells, thus possibly participating in the enhanced lymphocyte adhesion capacity that is implicated in the cardiovascular complications associated with diabetes or obesity. In both, the tissue origin of the soluble VAP-1/SSAO is unknown. We examined whether adipose tissue, which has abundant expression of VAP-1/SSAO, is a source of soluble VAP-1.

Methods

We detected VAP-1/SSAO in plasma of diabetic animals, with or without VAP-1 immunoprecipitation, and in culture medium from 3T3-L1 adipocytes and human adipose tissue explants. VAP-1 protein glycosylation was measured.

Results

Diabetic and obese animals have increased plasma SSAO activity associated with VAP-1 protein. We also found that 3T3-L1 adipocytes and human adipose tissue explants release a soluble form of VAP-1/SSAO, which derives from the membrane. The release of soluble VAP-1 was enhanced by exposure of murine and human adipocytes to TNF-α and blocked by batimastat, a metalloprotease inhibitor. Partial ablation of adipose tissue reduced plasma SSAO activity in normal and diabetic rats.

Conclusions/interpretation

Adipose cells are a source of soluble VAP-1/SSAO released by shedding of the membrane form. The release of SSAO is regulated by TNF-α and insulin. By releasing VAP-1/SSAO, adipose cells could contribute to the atherogenesis and vascular dysfunction associated with diabetes and obesity.

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Titel: Adipocytes release a soluble form of VAP-1/SSAO by a metalloprotease-dependent process and in a regulated manner
verfasst von: A. Abella
S. García-Vicente
N. Viguerie
A. Ros-Baró
M. Camps
M. Palacín
A. Zorzano
L. Marti
Publikationsdatum: 01.03.2004
Verlag: Springer Berlin Heidelberg
Erschienen in: Diabetologia / Ausgabe 3/2004
Print ISSN: 0012-186X
Elektronische ISSN: 1432-0428
DOI: https://doi.org/10.1007/s00125-004-1346-2

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