Deletion of endothelial adipose triglyceride lipase (ATGL) in mice led to neutral lipid accumulation, impaired vascular tone, and markedly increased lesion size in a model of atherosclerosis.
Endothelial ATGL plays a critical role in regulating fatty acid flux, maintaining endothelial cell homeostasis, and protecting against atherosclerosis.
Blood vessels are continually exposed to circulating lipids, and elevation of ApoB-containing lipoproteins causes atherosclerosis. Lipoprotein metabolism is highly regulated by lipolysis, largely at the level of the capillary endothelium lining metabolically active tissues. How large blood vessels, the site of atherosclerotic vascular disease, regulate the flux of fatty acids (FAs) into triglyceride-rich (TG-rich) lipid droplets (LDs) is not known. In this study, we showed that deletion of the enzyme adipose TG lipase (ATGL) in the endothelium led to neutral lipid accumulation in vessels and impaired endothelial-dependent vascular tone and nitric oxide synthesis to promote endothelial dysfunction. Mechanistically, the loss of ATGL led to endoplasmic reticulum stress-induced inflammation in the endothelium. Consistent with this mechanism, deletion of endothelial ATGL markedly increased lesion size in a model of atherosclerosis. Together, these data demonstrate that the dynamics of FA flux through LD affects endothelial cell homeostasis and consequently large vessel function during normal physiology and in a chronic disease state.
Boutagy et al. (Thu,) conducted a other in Atherosclerosis. Deletion of endothelial adipose triglyceride lipase (ATGL) vs. Control mice was evaluated on Endothelial dysfunction and atherosclerotic lesion size. Deletion of endothelial adipose triglyceride lipase (ATGL) in mice led to neutral lipid accumulation, impaired vascular tone, and markedly increased lesion size in a model of atherosclerosis.
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