Endothelial dysfunction in a mouse model of human neutral lipid storage disease
© Schrammel et al; licensee BioMed Central Ltd. 2013
Published: 29 August 2013
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 cardiomyocyte-restricted overexpression of ATGL (cardiac-rescued phenotype;
ATGL(-/-)/MHC-A35) we were able to differentiate between heart-related and -unrelated effects.
Endothelial dysfunction in murine ATGL deficiency partly arises from impaired cardiac contractility and originates from down-regulation of aortic eNOS presumably due to activation of the vascular proteasome. Potential heart-independent mechanisms contributing to the observed defect are currently investigated.
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