Dynamic metabolism of endothelial triglycerides protects against atherosclerosis in mice.

Autor:	Boutagy NE; Department of Pharmacology.; Vascular Biology and Therapeutics Program, and., Gamez-Mendez A; Department of Pharmacology.; Vascular Biology and Therapeutics Program, and., Fowler JW; Department of Pharmacology.; Vascular Biology and Therapeutics Program, and., Zhang H; Vascular Biology and Therapeutics Program, and.; Department of Comparative Medicine, Yale University School of Medicine, New Haven, Connecticut, USA., Chaube BK; Vascular Biology and Therapeutics Program, and.; Department of Comparative Medicine, Yale University School of Medicine, New Haven, Connecticut, USA., Esplugues E; Vascular Biology and Therapeutics Program, and.; Department of Comparative Medicine, Yale University School of Medicine, New Haven, Connecticut, USA., Kuo A; Vascular Biology Program, Department of Surgery, Boston Children's Hospital, Boston, Massachusetts, USA., Lee S; Department of Pharmacology.; Vascular Biology and Therapeutics Program, and., Horikami D; Department of Pharmacology.; Vascular Biology and Therapeutics Program, and., Zhang J; Department of Cardiology, Yale University School of Medicine, New Haven, Connecticut, USA., Citrin KM; Vascular Biology and Therapeutics Program, and.; Department of Comparative Medicine, Yale University School of Medicine, New Haven, Connecticut, USA., Singh AK; Department of Pharmacology.; Vascular Biology and Therapeutics Program, and., Coon BG; Cardiovascular Biology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma, USA.; Department of Cell Biology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, USA., Lee MY; Department of Physiology and Biophysics, Center for Cardiovascular Research, University of Illinois at Chicago School of Medicine, Chicago, Illinois, USA., Suarez Y; Vascular Biology and Therapeutics Program, and.; Department of Comparative Medicine, Yale University School of Medicine, New Haven, Connecticut, USA.; Department of Pathology, Yale University School of Medicine, New Haven, Connecticut, USA., Fernandez-Hernando C; Vascular Biology and Therapeutics Program, and.; Department of Comparative Medicine, Yale University School of Medicine, New Haven, Connecticut, USA.; Department of Pathology, Yale University School of Medicine, New Haven, Connecticut, USA., Sessa WC; Department of Pharmacology.; Vascular Biology and Therapeutics Program, and.; Department of Cardiology, Yale University School of Medicine, New Haven, Connecticut, USA.
Jazyk:	angličtina
Zdroj:	The Journal of clinical investigation [J Clin Invest] 2024 Jan 04; Vol. 134 (4). Date of Electronic Publication: 2024 Jan 04.
DOI:	10.1172/JCI170453
Abstrakt:	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.
Databáze:	MEDLINE
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