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Open Access | 10.1172/JCI173160
1Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States of America
2Institute for Translational Medicine and Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States of America
3Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States of America
4University of Pennsylvania, Philadelphia, United States of America
5Department of Systems Pharmacology and Translational Therapeutics, University of Pennsylvania, Philadelphia, United States of America
6Department of Systems Pharmacology and Translational Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States of America
Find articles by Kim, B. in: JCI | PubMed | Google Scholar
1Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States of America
2Institute for Translational Medicine and Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States of America
3Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States of America
4University of Pennsylvania, Philadelphia, United States of America
5Department of Systems Pharmacology and Translational Therapeutics, University of Pennsylvania, Philadelphia, United States of America
6Department of Systems Pharmacology and Translational Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States of America
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Zhao, W.
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1Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States of America
2Institute for Translational Medicine and Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States of America
3Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States of America
4University of Pennsylvania, Philadelphia, United States of America
5Department of Systems Pharmacology and Translational Therapeutics, University of Pennsylvania, Philadelphia, United States of America
6Department of Systems Pharmacology and Translational Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States of America
Find articles by Tang, S. in: JCI | PubMed | Google Scholar
1Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States of America
2Institute for Translational Medicine and Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States of America
3Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States of America
4University of Pennsylvania, Philadelphia, United States of America
5Department of Systems Pharmacology and Translational Therapeutics, University of Pennsylvania, Philadelphia, United States of America
6Department of Systems Pharmacology and Translational Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States of America
Find articles by Levin, M. in: JCI | PubMed | Google Scholar
1Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States of America
2Institute for Translational Medicine and Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States of America
3Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States of America
4University of Pennsylvania, Philadelphia, United States of America
5Department of Systems Pharmacology and Translational Therapeutics, University of Pennsylvania, Philadelphia, United States of America
6Department of Systems Pharmacology and Translational Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States of America
Find articles by Ibrahim, A. in: JCI | PubMed | Google Scholar
1Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States of America
2Institute for Translational Medicine and Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States of America
3Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States of America
4University of Pennsylvania, Philadelphia, United States of America
5Department of Systems Pharmacology and Translational Therapeutics, University of Pennsylvania, Philadelphia, United States of America
6Department of Systems Pharmacology and Translational Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States of America
Find articles by Yang, Y. in: JCI | PubMed | Google Scholar
1Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States of America
2Institute for Translational Medicine and Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States of America
3Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States of America
4University of Pennsylvania, Philadelphia, United States of America
5Department of Systems Pharmacology and Translational Therapeutics, University of Pennsylvania, Philadelphia, United States of America
6Department of Systems Pharmacology and Translational Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States of America
Find articles by Roberts, E. in: JCI | PubMed | Google Scholar
1Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States of America
2Institute for Translational Medicine and Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States of America
3Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States of America
4University of Pennsylvania, Philadelphia, United States of America
5Department of Systems Pharmacology and Translational Therapeutics, University of Pennsylvania, Philadelphia, United States of America
6Department of Systems Pharmacology and Translational Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States of America
Find articles by Lai, L. in: JCI | PubMed | Google Scholar
1Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States of America
2Institute for Translational Medicine and Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States of America
3Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States of America
4University of Pennsylvania, Philadelphia, United States of America
5Department of Systems Pharmacology and Translational Therapeutics, University of Pennsylvania, Philadelphia, United States of America
6Department of Systems Pharmacology and Translational Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States of America
Find articles by Li, J. in: JCI | PubMed | Google Scholar
1Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States of America
2Institute for Translational Medicine and Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States of America
3Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States of America
4University of Pennsylvania, Philadelphia, United States of America
5Department of Systems Pharmacology and Translational Therapeutics, University of Pennsylvania, Philadelphia, United States of America
6Department of Systems Pharmacology and Translational Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States of America
Find articles by Assoian, R. in: JCI | PubMed | Google Scholar
1Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States of America
2Institute for Translational Medicine and Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States of America
3Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States of America
4University of Pennsylvania, Philadelphia, United States of America
5Department of Systems Pharmacology and Translational Therapeutics, University of Pennsylvania, Philadelphia, United States of America
6Department of Systems Pharmacology and Translational Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States of America
Find articles by FitzGerald, G. in: JCI | PubMed | Google Scholar
1Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States of America
2Institute for Translational Medicine and Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States of America
3Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States of America
4University of Pennsylvania, Philadelphia, United States of America
5Department of Systems Pharmacology and Translational Therapeutics, University of Pennsylvania, Philadelphia, United States of America
6Department of Systems Pharmacology and Translational Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States of America
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Arany, Z.
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Published October 12, 2023 - More info
The metabolic syndrome, today affecting more than 20% of the US population, is a group of five conditions that often co-exist and that strongly predispose to cardiovascular disease. How these conditions are linked mechanistically remains unclear, especially two of these: obesity and elevated blood pressure. Here we show that high fat consumption in mice leads to the accumulation of lipid droplets in endothelial cells throughout the organism, and that lipid droplet accumulation in endothelium suppresses endothelial nitric oxide synthase (eNOS), reduces NO production, elevates blood pressure, and accelerates atherosclerosis. Mechanistically, the accumulation of lipid droplets destabilizes eNOS mRNA and activates an endothelial inflammatory signaling cascade that suppresses eNOS and NO production. Pharmacological prevention of lipid droplet formation reverses the suppression of NO production in cell culture and in vivo, and blunts blood pressure elevation in response to high fat diet. These results highlight lipid droplets as a critical and unappreciated component of endothelial cell biology, explain how lipids increase blood pressure acutely, and provide a mechanistic account for the epidemiological link between obesity and elevated blood pressure.