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Endothelial dysfunction in adipose triglyceride lipase deficiency.
Schrammel, Astrid; Mussbacher, Marion; Wölkart, Gerald; Stessel, Heike; Pail, Karoline; Winkler, Sarah; Schweiger, Martina; Haemmerle, Guenter; Al Zoughbi, Wael; Höfler, Gerald; Lametschwandtner, Alois; Zechner, Rudolf; Mayer, Bernd.
Afiliação
  • Schrammel A; Department of Pharmacology and Toxicology, University of Graz, Universitätsplatz 2, 8010 Graz, Austria. Electronic address: astrid.schrammel-gorren@uni-graz.at.
  • Mussbacher M; Department of Pharmacology and Toxicology, University of Graz, Universitätsplatz 2, 8010 Graz, Austria. Electronic address: marion.mussbacher@uni-graz.at.
  • Wölkart G; Department of Pharmacology and Toxicology, University of Graz, Universitätsplatz 2, 8010 Graz, Austria. Electronic address: gerald.woelkart@uni-graz.at.
  • Stessel H; Department of Pharmacology and Toxicology, University of Graz, Universitätsplatz 2, 8010 Graz, Austria. Electronic address: heike.stessel@uni-graz.at.
  • Pail K; Department of Pharmacology and Toxicology, University of Graz, Universitätsplatz 2, 8010 Graz, Austria. Electronic address: karoline.pail@uni-graz.at.
  • Winkler S; Department of Pharmacology and Toxicology, University of Graz, Universitätsplatz 2, 8010 Graz, Austria. Electronic address: sarah.winkler@uni-graz.at.
  • Schweiger M; Department of Molecular Biosciences, University of Graz, Heinrichstrasse 31, 8010 Graz, Austria. Electronic address: tina.schweiger@uni-graz.at.
  • Haemmerle G; Department of Molecular Biosciences, University of Graz, Heinrichstrasse 31, 8010 Graz, Austria. Electronic address: guenter.haemmerle@uni-graz.at.
  • Al Zoughbi W; Institute of Pathology, Medical University of Graz, Auenbruggerplatz 25, 8010 Graz, Austria. Electronic address: wael.alzoughbi@stud.medunigraz.at.
  • Höfler G; Institute of Pathology, Medical University of Graz, Auenbruggerplatz 25, 8010 Graz, Austria. Electronic address: gerald.hoefler@medunigraz.at.
  • Lametschwandtner A; Department of Cell Biology and Physiology, Vessel and Muscle Research Unit, University of Salzburg, Hellbrunnerstrasse 34, 5020 Salzburg, Austria. Electronic address: Alois.Lametschwandtner@sbg.ac.at.
  • Zechner R; Department of Molecular Biosciences, University of Graz, Heinrichstrasse 31, 8010 Graz, Austria. Electronic address: rudolf.zechner@uni-graz.at.
  • Mayer B; Department of Pharmacology and Toxicology, University of Graz, Universitätsplatz 2, 8010 Graz, Austria. Electronic address: mayer@uni-graz.at.
Biochim Biophys Acta ; 1841(6): 906-17, 2014 Jun.
Article em En | MEDLINE | ID: mdl-24657704
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.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Triglicerídeos / Metabolismo dos Lipídeos / Insuficiência Cardíaca / Lipase / Obesidade Limite: Animals / Humans Idioma: En Revista: Biochim Biophys Acta Ano de publicação: 2014 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Triglicerídeos / Metabolismo dos Lipídeos / Insuficiência Cardíaca / Lipase / Obesidade Limite: Animals / Humans Idioma: En Revista: Biochim Biophys Acta Ano de publicação: 2014 Tipo de documento: Article