Endothelial Glycocalyx Turnover in Vascular Health and Disease: Rethinking Endothelial Dysfunction

  • Annu Rev Biochem. 2025 Jun;94(1):561-586. doi: 10.1146/annurev-biochem-032620-104745.
Alejandro Gomez Toledo  1 ,  Gregory J Golden  2 ,  Richard D Cummings  3 ,  Johan Malmström  1 ,  Jeffrey D Esko  2
Affiliations
  • 1. Department of Clinical Sciences, Lund University, Lund, Sweden.
  • 2. Department of Cellular and Molecular Medicine and Glycobiology Research and Training Center, University of California, San Diego, La Jolla, California, USA; email: [email protected].
  • 3. Department of Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA.
Abstract

The endothelial glycocalyx, a glycan-rich layer on the luminal surface of endothelial cells lining blood and lymphatic vessels, plays a crucial role in vascular homeostasis by regulating vascular permeability, immune cell trafficking, and vascular tone. Dysregulated endothelial glycocalyx turnover-whether through altered synthesis, intracellular degradation, or shedding-contributes to endothelial dysfunction in conditions such as Sepsis, ischemic events, and chronic inflammatory disorders including diabetes and Atherosclerosis. In this review, we examine the structure, function, and turnover of the endothelial glycocalyx, emphasizing how pathological changes in its turnover drive vascular dysfunction. We also highlight diagnostic approaches to evaluate dysregulated endothelial glycocalyx turnover in connection with vascular diseases and discuss therapeutic strategies aimed at preventing endothelial glycocalyx degradation and restoring endothelial function.

Keywords
endothelium; extracellular matrix; glycocalyx; infection; inflammation; vasculature.