Primary endothelial dysfunction: atherosclerosis

J Mol Cell Cardiol. 1999 Jan;31(1):23-37. doi: 10.1006/jmcc.1998.0841.


The endothelium synthesizes and releases several vasodilating factors, including nitric oxide, endothelium-derived hyperpolarizing factor, and prostacyclin. Under certain conditions, it also liberates vasocontracting factors. Thus, the endothelium plays an important role in regulating vascular homeostasis. Several intracellular mechanisms are involved in the synthesis of nitric oxide, including receptor-coupled G proteins, the availability of L-arginine, cofactors for endothelial nitric oxide synthase and the expression of the enzyme. Endothelial dysfunction by aging, menopause and hypercholesterolemia is involved in the development of atherosclerotic vascular lesions, and predisposes the blood vessel to several vascular disorders, such as vasospasm and thrombosis. Multiple mechanisms are apparently involved in the pathogenesis of the endothelial dysfunction in atherosclerosis. The reduced production of nitric oxide by the endothelium is caused by abnormalities in endothelial signal transduction, availability of L-arginine, cofactors for endothelial nitric oxide synthase and expression of the enzyme. Other mechanisms may also be involved in the impaired endothelium-dependent relaxations in atherosclerosis, including increased destruction of nitric oxide by superoxide anion, altered responsiveness of vascular smooth muscle, and concomitant release of vasocontracting factors. In addition to the treatment of the underlying risk factors, several pharmacological agents can improve endothelial dysfunction in atherosclerosis. Thus, the endothelium is a novel therapeutic target for the treatment of atherosclerotic cardiovascular disease.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Animals
  • Arteriosclerosis / physiopathology*
  • Biological Factors / physiology
  • Cell Division
  • Endothelins / physiology
  • Endothelium, Vascular / physiopathology*
  • Epoprostenol / physiology
  • Humans
  • Hypercholesterolemia / metabolism
  • Menopause / metabolism
  • Models, Biological
  • Muscle, Smooth, Vascular / metabolism
  • Nitric Oxide / biosynthesis
  • Nitric Oxide / physiology
  • Nitric Oxide Synthase / metabolism
  • Nitric Oxide Synthase / physiology
  • Rabbits
  • Swine


  • Biological Factors
  • Endothelins
  • endothelium-dependent hyperpolarization factor
  • Nitric Oxide
  • Epoprostenol
  • Nitric Oxide Synthase