Endothelial dysfunction in adipose triglyceride lipase deficiency

• DOI: 10.1016/j.bbalip.2014.03.005
• Publication Date: 2014-03-22T05:53:27Z
• Authors: Astrid Schrammel; Marion Mussbacher; Gerald Wölkart; Heike Stessel; Karoline Pail; Sarah Winkler; Martina Schweiger; Guenter Haemmerle; Wael Al Zoughbi; Gerald Höfler; Alois Lametschwan...; Rudolf Zechner; Bernd Mayer
• Keywords: Adipose triglyceride lipase; Knockout mouse; Endothelial Dysfunction

Systemic knockout of adipose triglyceride lipase (ATGL), the pivotal enzyme lipolysis, results in a murine phenotype that is characterized by progredient cardiac steatosis and severe heart failure. Since vascular dysfunction have been closely related numerous studies we investigated endothelium-dependent -independent vessel function ATGL mice. Aortic relaxation Langendorff perfusion experiments isolated hearts showed mice suffer from pronounced micro- macrovascular endothelial dysfunction. Experiments with agonists directly targeting smooth muscle cells revealed functional integrity cell layer. Loss reactivity was restored ~50% upon treatment PPARα agonist Wy14,643, indicating this phenomenon partly consequence impaired contractility. Biochemical analysis aortic NO synthase expression activity were significantly reduced deficiency. Enzyme fully treated agonist. perivascular tissue demonstrated inflammatory oxidative stress which occurs independent might contribute to defects. Our reveal hitherto unrecognized link between disturbed lipid metabolism, obesity cardiovascular disease.