Abstract
Background Systemic knockout of adipose triglyceride lipase (ATGL), the rate-limiting enzyme of triglyceride catabolism, results in a murine phenotype characterized by progressive accumulation of lipids in the heart finally leading to lethal cardiac dysfunction. Since cardiac and vascular dysfunction are closely related we investigated endothelium-dependent and -independent vessel function of ATGL knockout (ATGL(-/-)) mice. Using mice with cardiomyocyterestricted overexpression of ATGL (cardiac-rescued phenotype; ATGL(-/-)/MHC-A35) we were able to differentiate between heart-related and -unrelated effects. Results Aortic relaxation studies and Langendorff perfusion experiments of isolated hearts demonstrated that ATGL (-/-) mice suffer from pronounced microand macrovascular endothelial dysfunction. Experiments with DEA/NO revealed the functional integrity of the smooth muscle cell layer. Since loss in vascular reactivity was restored by ~50 % in cardiac-rescued mice, this phenomenon seems partly a consequence of impaired cardiac contractility. Biochemical analysis revealed that aortic eNOS protein was down-regulated by more than 60% in aortas of ATGL (-/-) mice. As consequence, phosphorylation of VASP at Ser 239 was almost abolished. Both parameters were
Highlights
Systemic knockout of adipose triglyceride lipase (ATGL), the rate-limiting enzyme of triglyceride catabolism, results in a murine phenotype characterized by progressive accumulation of lipids in the heart leading to lethal cardiac dysfunction
Aortic relaxation studies and Langendorff perfusion experiments of isolated hearts demonstrated that ATGL (-/-) mice suffer from pronounced micro- and macrovascular endothelial dysfunction
Since loss in vascular reactivity was restored by ~50 % in cardiac-rescued mice, this phenomenon seems partly a consequence of impaired cardiac contractility
Summary
Endothelial dysfunction in a mouse model of human neutral lipid storage disease Astrid Schrammel1*, Marion Mussbacher, Gerald Wölkart, Heike Stessel, Günter Hämmerle, Wael Al Zoughbi, Gerald Höfler, Alois Lametschwandtner, Rudolf Zechner, Bernd Mayer. From 6th International Conference on cGMP: Generators, Effectors and Therapeutic Implications Erfurt, Germany. From 6th International Conference on cGMP: Generators, Effectors and Therapeutic Implications Erfurt, Germany. 28-30 June 2013
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
