2. Academic Validation
  3. Endothelial lipid droplets suppress eNOS to link high fat consumption to blood pressure elevation

Endothelial lipid droplets suppress eNOS to link high fat consumption to blood pressure elevation

  • J Clin Invest. 2023 Oct 12:e173160. doi: 10.1172/JCI173160.
Boa Kim 1,  Wencao Zhao 1,  Soon Yew Tang 2,  Michael G Levin 3,  Ayon Ibrahim 3,  Yifan Yang 3,  Emilia M Roberts 4,  Ling Lai 3,  Jian Li 3,  Richard K Assoian 5,  Garret A FitzGerald 6,  Zoltan Arany 3
Affiliations

Affiliations

  • 1 Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States of America.
  • 2 Institute for Translational Medicine and Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States of America.
  • 3 Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States of America.
  • 4 University of Pennsylvania, Philadelphia, United States of America.
  • 5 Department of Systems Pharmacology and Translational Therapeutics, University of Pennsylvania, Philadelphia, United States of America.
  • 6 Department of Systems Pharmacology and Translational Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States of America.
PMID: 37824206 DOI: 10.1172/JCI173160
Abstract

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.

Keywords

Cardiology; Endothelial cells.

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