1. Dynamic metabolism of endothelial triglycerides protects against atherosclerosis in mice
- Author
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Boutagy, Nabil E., Gamez-Mendez, Ana, Fowler, Joseph W.M., Zhang, Hanming, Chaube, Bal K., Esplugues, Enric, Kuo, Andrew, Lee, Sungwoon, Horikami, Daiki, Zhang, Jiasheng, Citrin, Kathryn M., Singh, Abhishek K., Coon, Brian G., Lee, Monica Y., Suarez, Yajaira, Fernandez-Hernando, Carlos, and Sessa, William C.
- Subjects
Lipids -- Physiological aspects ,Chronic diseases -- Physiological aspects ,Endothelium -- Physiological aspects ,Antilipemic agents -- Physiological aspects ,Lipase -- Physiological aspects ,Nitric oxide -- Physiological aspects ,Blood circulation disorders -- Physiological aspects ,Atherosclerosis -- Physiological aspects ,Health care industry - Abstract
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 endothelialdependent 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., Introduction The vascular endothelium is essential in lipid partitioning (1). Specifically, in metabolically active tissues (e.g., heart, skeletal muscle, adipose), triglyceride-rich (TG-rich) lipoproteins (chylomicrons, VLDL) are metabolized by lipoprotein lipase [...]
- Published
- 2024
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