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Emerging regulators of endothelial lipid metabolism in atherosclerosis

Jason S Irei1, Kai Hirayama, William A Boisvert

  • 1Center for Cardiovascular Research, John A. Burns School of Medicine, University of Hawaii, Honolulu, Hawaii, USA.

Current Opinion in Lipidology
|February 28, 2026
PubMed

Insights

Elevated palmitic acid disrupts endothelial cell function, impacting cardiovascular health. Understanding endothelial lipid metabolism is crucial for developing new atherosclerosis treatments.

Area of Science:

  • Cardiovascular Research
  • Cell Biology
  • Metabolic Research

Background:

  • Cardiovascular disease (CVD) risk remains high despite effective hyperlipidemia and hypertension therapies.
  • Endothelial cells (ECs) play a critical role in the development and progression of atherosclerotic CVD.
  • Current research focuses on endothelial lipid metabolism to understand and mitigate CVD risk.

Purpose of the Study:

  • To review current research on endothelial lipid metabolism.
  • To emphasize the role of endothelial lipid metabolism in atherosclerosis.
  • To update on mechanisms of endothelial dysfunction.

Main Methods:

  • Literature review of recent studies on endothelial lipid metabolism.
  • Analysis of molecular mechanisms linking lipid metabolism to endothelial function.
  • Examination of the role of palmitic acid and cholesterol in endothelial homeostasis.

Main Results:

  • Elevated palmitic acid (PA) negatively impacts endothelial cells by affecting pyruvate kinase isozyme M2 (PKM2) activity.
  • PA is essential for endothelial ciliation and cell health, but its dysregulation is detrimental.
  • Endothelial cholesterol metabolism and hemodynamic forces are key regulators of endothelial homeostasis; their perturbation leads to dysfunction and lipid accumulation.

Conclusions:

  • Atherosclerosis is a complex disease involving multiple cell types and dysfunction.
  • Significant progress has been made in understanding endothelial lipid metabolism.
  • Further research is needed to identify therapeutic targets for reducing cardiovascular disease risk.
Abstract

Keywords:
atherosclerosischolesterolendothelial cellspalmitic acidshear stress

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