Endothelial Dysfunction - The Endothelium

The Endothelium

Dicken Weatherby, N.D. and Beth Ellen DiLuglio, MS, RDN, LDN

The endothelium is a thin single-cell layer that forms the inner lining of blood vessels (capillaries, veins, and arteries), as well as the lymphatic system.

This thin layer performs sizable functions including a custodial role in [i] [ii] [iii]

  • Angiogenesis
  • Blood fluidity
  • Fibrosis
  • Immune regulation
  • Inflammation
  • Modulation of leukocyte adhesion
  • Platelet activation and aggregation
  • Smooth muscle cell proliferation
  • Thrombosis
  • Vascular tone and blood flow
  • Vasoactive hormone synthesis (e.g., angiotensin II)
  • Vasomotor tone (via angiotensinogen, endothelin, nitric oxide, and prostacyclin)
  • Wound healing

Within blood vessels, the endothelium regulates blood flow by sending relaxation/constriction messages to vascular smooth muscle cells.[iv] It also serves as a barrier that protects the smooth muscle, found in the middle of the artery, from toxic metabolites in the blood. When these toxic metabolites, such as homocysteine, chlorine, environmental pollutants, free radicals, and smoking (including e-cigarettes) damage smooth muscle cells, the process of atherosclerosis is initiated.[v] [vi] [vii] [viii] [ix]

The protective sentinel of the endothelium is the endothelial glycocalyx, a mesh-like barrier that protects the interior endothelial lining. It comprises membrane-bound endothelial and plasma-derived molecules, including glycoproteins, glycosaminoglycans, and proteoglycans. Hyaluronic acid, thrombomodulin, superoxide-dismutase, and antithrombin III can be found in this dynamic complex layer. Ongoing research suggests the endothelial glycocalyx plays a major role in the homeostasis of the blood vessel wall.[x]

The vascular endothelium can be considered the largest endocrine organ in the body due to its abundant production of vasoactive substances and its balancing act between[xi]

  • Antioxidation and pro-oxidation
  • Growth inhibition and growth promotion
  • Anti-thrombosis and pro-thrombosis
  • Anti-inflammation and pro-inflammation
  • Vasodilation and vasoconstriction
    • Vasodilation is mediated by nitric oxide, endothelium-derived hyperpolarizing factor (EDHF), and prostacyclin.
    • Vasoconstriction is mediated by angiotensin II, endothelin-1 (ET-1), prostaglandin H-2, and thromboxane.[xii]

Research

[i] Al-Qaisi, Mo et al. “Measurement of endothelial function and its clinical utility for cardiovascular risk.” Vascular health and risk management vol. 4,3 (2008): 647-52.

[ii] Félétou, Michel. The Endothelium: Part 1: Multiple Functions of the Endothelial Cells—Focus on Endothelium-Derived Vasoactive Mediators. Morgan & Claypool Life Sciences, 2011. 

[iii] Widmer, R Jay, and Amir Lerman. “Endothelial dysfunction and cardiovascular disease.” Global cardiology science & practice vol. 2014,3 291-308. 16 Oct. 2014.

[iv] Barthelmes, Jens et al. “Endothelial dysfunction in cardiovascular disease and Flammer syndrome-similarities and differences.” The EPMA journal vol. 8,2 99-109. 6 Jun. 2017.

[v] Valavanidis, Athanasios et al. “Tobacco smoke: involvement of reactive oxygen species and stable free radicals in mechanisms of oxidative damage, carcinogenesis and synergistic effects with other respirable particles.” International journal of environmental research and public health vol. 6,2 (2009): 445-62. 

[vi] Miller, Mark R. “Oxidative stress and the cardiovascular effects of air pollution.” Free radical biology & medicine vol. 151 (2020): 69-87. 

[vii] Roberto Carnevale, Vittoria Cammisotto, Francesca Pagano and Cristina Nocella (November 5th 2018). Effects of Smoking on Oxidative Stress and Vascular Function, Smoking Prevention and Cessation, Mirjana Rajer, IntechOpen

[viii] Honavar, Jaideep et al. “Chlorine gas exposure causes systemic endothelial dysfunction by inhibiting endothelial nitric oxide synthase-dependent signaling.” American journal of respiratory cell and molecular biology vol. 45,2 (2011): 419-25. 

[ix] Goncharov, Alexey et al. “Blood pressure in relation to concentrations of PCB congeners and chlorinated pesticides.” Environmental health perspectives vol. 119,3 (2011): 319-25. 

[x] Reitsma, Sietze et al. “The endothelial glycocalyx: composition, functions, and visualization.” Pflugers Archiv : European journal of physiology vol. 454,3 (2007): 345-59. 

[xi] Higashi, Yukihito. “Assessment of endothelial function. History, methodological aspects, and clinical perspectives.” International heart journal vol. 56,2 (2015): 125-34. 

[xii] Park, Kyoung-Ha, and Woo Jung Park. “Endothelial Dysfunction: Clinical Implications in Cardiovascular Disease and Therapeutic Approaches.” Journal of Korean medical science vol. 30,9 (2015): 1213-25. 

[xiii] Sitia, S et al. “From endothelial dysfunction to atherosclerosis.” Autoimmunity reviews vol. 9,12 (2010): 830-4.

[xiv] Félétou, Michel. The Endothelium: Part 1: Multiple Functions of the Endothelial Cells—Focus on Endothelium-Derived Vasoactive Mediators. Morgan & Claypool Life Sciences, 2011. [xv] Félétou, Michel. The Endothelium: Part 1: Multiple Functions of the Endothelial Cells—Focus on Endothelium-Derived Vasoactive Mediators. Morgan & Claypool Life Sciences, 2011. 

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