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This article is part of the supplement: 18th Scientific Symposium of the Austrian Pharmacological Society (APHAR)

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Role of perivascular adipose tissue in endothelial dysfunction of adipose triglyceride lipase-deficient mice

Karoline Pail1, Sarah Winkler1, Gerald Wölkart1, Günter Hämmerle2, Rudolf Zechner2, Alois Lametschwandtner3, Bernd Mayer1 and Astrid Schrammel1*

Author affiliations

1 Department of Pharmacology and Toxicology, Institute of Pharmaceutical Sciences, University of Graz, 8010 Graz, Austria

2 Institute of Molecular Biosciences, University of Graz, 8010 Graz, Austria

3 Division of Zoology and Functional Anatomy, Vessel and Muscle Research Unit, University of Salzburg, 5020 Salzburg, Austria

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Citation and License

BMC Pharmacology and Toxicology 2012, 13(Suppl 1):A18  doi:10.1186/2050-6511-13-S1-A18

The electronic version of this article is the complete one and can be found online at:

Published:17 September 2012

© 2012 Pail et al; licensee BioMed Central Ltd.

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Perivascular adipose tissue (PVAT) has been recognized as an important factor in vascular biology due to its ability to produce a variety of vasoactive substances. In addition, it is regarded as an important source of proinflammatory mediators and reactive oxygen species (ROS). Experiments from our laboratory demonstrated that mice lacking adipose triglyceride lipase (ATGL), a crucial enzyme of triglyceride catabolism, suffer from severe micro- and macrovascular endothelial dysfunction. Since blood vessels of ATGL knockout mice (ATGL(−/−) mice) are surrounded by large amounts of PVAT, we investigated its potential contribution to the observed endothelial dysfunction.

Methods and results

PVAT encompassing thoracic aortas of wild-type (WT) and ATGL(−/−) mice was isolated, characterized, and analyzed for protein and mRNA expression of different adipokines, inflammation markers, and sources of oxidative stress using real-time PCR and Western blot analysis, respectively. Knockout of ATGL caused a 7-fold increase in PVAT wet weight. While mRNA expression of adiponectin was reduced to about 50%, leptin mRNA was increased about 4-fold in ATGL deficiency. Adipose mRNA levels of the inflammation markers tumor necrosis factor alpha (TNF-α), monocyte chemoattractant protein 1 (MCP-1), and interleukin-6 (IL-6) were about 5-fold higher in ATGL-deficient PVAT. In addition, the NOX2/p67phox complex was significantly upregulated at protein level. Heme oxygenase-1, which has been described protective against oxidative and inflammatory stress, was increased about 5-fold in ATGL deficiency. To distinguish between direct PVAT-mediated effects and those originating from the cardiac dysfunctional phenotype of the animals, we additionally analyzed tissue isolated from ATGL(−/−) mice with cardiomyocyte-specific overexpression of ATGL (rescued cardiac phenotype). Interestingly, the effect of ATGL knockout on TNF-α and leptin expression was reversible. By contrast, increased adipose NOX2/p67phox, MCP-1 and IL-6 expression persisted even upon restoration of cardiac function.


Our data indicate that PVAT-derived inflammatory and NADPH oxidase-mediated oxidative stress might contribute to endothelial dysfunction in ATGL deficiency. The functional consequences of these findings are currently being investigated in our laboratory.


This work was supported by the FWF Austrian Science Fund (grants F3003, P24005).