Glycocalyx in Atherosclerosis-Relevant Endothelium Function and as a Therapeutic Target

Curr Atheroscler Rep. 2017 Nov 10;19(12):63. doi: 10.1007/s11883-017-0691-9.


Purpose of review: The cell surface-attached extracellular glycocalyx (GCX) layer is a major contributor to endothelial cell (EC) function and EC-dependent vascular health and is a first line of defense against vascular diseases including atherosclerosis. Here, we highlight our findings regarding three GCX-dependent EC functions, which are altered when GCX is shed and in atherosclerosis. We discuss why the GCX is a viable option for the prevention and treatment of atherosclerosis.

Recent findings: GCX regulated EC activities such as barrier and filtration function, active cell-to-cell communication, and vascular tone mediation contribute to function of the entire vascular wall. Atheroprone vessel regions, including bifurcation sites, exhibit breakdown in GCX. This GCX degradation allows increased lipid flux and thereby promotes lipid deposition in the vessel walls, a hallmark of atherosclerosis. GCX degradation also alters EC-to-EC communication while increasing EC-to-inflammatory cell interactions that enable inflammatory cells to migrate into the vessel wall. Inflammatory macrophages and foam cells, to be specific, appear in early stages of atherosclerosis. Furthermore, GCX degradation deregulates vascular tone, by causing ECs to reduce their expression of endothelial nitric oxide synthase (eNOS) which produces the vasodilator, nitric oxide. Loss of vasodilation supports vasoconstriction, which promotes the progression of atherosclerosis. Common medicinal atherosclerosis therapies include lipid lowering and anti-platelet therapies. None of these treatments specifically target the endothelial GCX, although the GCX is at the front-line in atherosclerosis combat. This review demonstrates the viability of targeting the GCX therapeutically, to support proper EC functionality and prevent and/or treat atherosclerosis.

Keywords: Atherosclerosis; Cardiovascular disease treatment; Endothelial dysfunction; Endothelial glycocalyx.

Publication types

  • Review

MeSH terms

  • Animals
  • Atherosclerosis / etiology
  • Atherosclerosis / metabolism
  • Atherosclerosis / physiopathology*
  • Atherosclerosis / therapy
  • Endothelial Cells / metabolism*
  • Endothelial Cells / physiology
  • Endothelium, Vascular / metabolism*
  • Endothelium, Vascular / physiology
  • Endothelium, Vascular / physiopathology
  • Glycocalyx / metabolism*
  • Glycocalyx / physiology
  • Humans
  • Models, Animal
  • Molecular Targeted Therapy