Homocysteine and glutathione peroxidase-1

Antioxid Redox Signal. 2007 Nov;9(11):1923-40. doi: 10.1089/ars.2007.1771.


Mildly elevated homocysteine levels (Hcy) increase the risk for atherothrombotic vascular disease in the coronary, cerebrovascular, and peripheral arterial circulations. The molecular mechanisms responsible for decreased bioavailability of endothelium-derived nitric oxide (NO) by Hcy involve an increase of vascular oxidant stress and inhibition of important antioxidant capacity. Glutathione peroxidase-1 (GPx-1), a selenocysteine-containing antioxidant enzyme, may be a key target of Hcy's deleterious actions, and several experimental and clinical studies have demonstrated a complex relationship between plasma total homocysteine (tHcy), GPx-1, and endothelial dysfunction. Hcy may promote endothelial dysfunction, in part by decreasing GPx-1 expression; however, there is evidence to suggest that overexpression of GPx-1 can compensate for these effects. This review summarizes the current knowledge of the metabolism of Hcy, the effects of hyperhomocysteinemia observed in in vitro and in vivo models that lead to endothelial dysfunction and the possible mechanisms for these actions, and the role of GPx-1 in the pathogenesis of Hcy-induced cardiovascular disease (CVD).

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Atherosclerosis / blood
  • Atherosclerosis / epidemiology
  • Biological Availability
  • Endothelium, Vascular / metabolism
  • Endothelium, Vascular / pathology
  • Evidence-Based Medicine
  • Glutathione Peroxidase / blood
  • Glutathione Peroxidase / metabolism*
  • Homocysteine / blood
  • Homocysteine / metabolism*
  • Humans
  • Hyperhomocysteinemia / blood
  • Hyperhomocysteinemia / epidemiology
  • Models, Biological
  • Muscle, Smooth, Vascular / metabolism
  • Muscle, Smooth, Vascular / pathology
  • Nitric Oxide / metabolism
  • Nitric Oxide / pharmacokinetics
  • Thrombosis / blood
  • Thrombosis / epidemiology


  • Homocysteine
  • Nitric Oxide
  • Glutathione Peroxidase