Dynamic metabolism of endothelial triglycerides protects against atherosclerosis in mice

Dynamic metabolism of endothelial triglycerides protects against atherosclerosis in mice

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,...

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Bibliographic Details
Published in:The Journal of clinical investigation Vol. 134; no. 4; pp. 1 - 12
Main Authors: Boutagy, Nabil E, Gamez-Mendez, Ana, Fowler, Joseph W M, Zhang, Hanming, Chaube, Bal K, Esplugues, Enric, Kuo, Andrew, Lee, Sungwoon, Morikami, Daiki, Zhang, Jiasheng, Citrin, Kathryn M, Singh, Abhishek K, Coon, Brian G, Lee, Monica Y, Suarez, Vajaira, Fernandez-Hernando, Carlos, Sessa, William C
Format: Journal Article
Language:English
Published: Ann Arbor American Society for Clinical Investigation 01-02-2024
Subjects:
Arteriosclerosis
Atherosclerosis
Blood vessels
Chronic illnesses
Coronary vessels
Endoplasmic reticulum
Endothelial cells
Endothelium
Enzymes
Fatty acids
Genes
Homeostasis
Lipid metabolism
Lipids
Lipolysis
Lipoproteins
Metabolism
Metabolites
Musculoskeletal system
Mutation
Nitric oxide
Physiology
Proteins
Transgenic animals
Triglycerides
Vascular diseases
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Summary: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 (ATCL) 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 ATCL led to endoplasmic reticulum stress-induced inflammation in the endothelium. Consistent with this mechanism, deletion of endothelial ATCL 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.
ISSN:0021-9738
1558-8238
DOI:10.1172/JCI176347