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Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Schrammel, A; Mussbacher, M; Wölkart, G; Stessel, H; Pail, K; Winkler, S; Schweiger, M; Haemmerle, G; Al Zoughbi, W; Höfler, G; Lametschwandtner, A; Zechner, R; Mayer, B.
Endothelial dysfunction in adipose triglyceride lipase deficiency.
Biochim Biophys Acta. 2014; 1841(6):906-917
Doi: 10.1016/j.bbalip.2014.03.005
[OPEN ACCESS]
Web of Science
PubMed
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- Co-Autor*innen der Med Uni Graz
- Al-Zoughbi Wael
- Höfler Gerald
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- Abstract:
- Systemic knockout of adipose triglyceride lipase (ATGL), the pivotal enzyme of triglyceride lipolysis, results in a murine phenotype that is characterized by progredient cardiac steatosis and severe heart failure. Since cardiac and vascular dysfunction have been closely related in numerous studies we investigated endothelium-dependent and -independent vessel function of ATGL knockout mice. Aortic relaxation studies and Langendorff perfusion experiments of isolated hearts showed that ATGL knockout mice suffer from pronounced micro- and macrovascular endothelial dysfunction. Experiments with agonists directly targeting vascular smooth muscle cells revealed the functional integrity of the smooth muscle cell layer. Loss of vascular reactivity was restored ~50% upon treatment of ATGL knockout mice with the PPARα agonist Wy14,643, indicating that this phenomenon is partly a consequence of impaired cardiac contractility. Biochemical analysis revealed that aortic endothelial NO synthase expression and activity were significantly reduced in ATGL deficiency. Enzyme activity was fully restored in ATGL mice treated with the PPARα agonist. Biochemical analysis of perivascular adipose tissue demonstrated that ATGL knockout mice suffer from perivascular inflammatory oxidative stress which occurs independent of cardiac dysfunction and might contribute to vascular defects. Our results reveal a hitherto unrecognized link between disturbed lipid metabolism, obesity and cardiovascular disease. Copyright © 2014 The Authors. Published by Elsevier B.V. All rights reserved.
- Find related publications in this database (using NLM MeSH Indexing)
- Adipose Tissue - enzymology
- Adipose Tissue - metabolism
- Animals -
- Disease Models, Animal -
- Gene Expression Regulation, Enzymologic -
- Heart Failure - enzymology
- Heart Failure - pathology
- Humans -
- Lipase - biosynthesis
- Lipase - genetics
- Lipase - metabolism
- Lipid Metabolism - genetics
- Mice -
- Mice, Knockout -
- Myocytes, Smooth Muscle - metabolism
- Myocytes, Smooth Muscle - pathology
- Nitric Oxide Synthase - biosynthesis
- Obesity - enzymology
- Obesity - genetics
- Obesity - pathology
- Organ Culture Techniques -
- Oxidative Stress -
- PPAR alpha - genetics
- PPAR alpha - metabolism
- Triglycerides - metabolism
- Find related publications in this database (Keywords)
- Adipose triglyceride lipase
- Endothelial dysfunction
- Perivascular inflammation
- Endothelial NO synthase
- Vascular proteasome