Hyperhomocysteinemia and its role in the development of atherosclerosis

Clin Biochem. 2003 Sep;36(6):431-41. doi: 10.1016/s0009-9120(03)00062-6.


Numerous epidemiological studies have demonstrated that hyperhomocysteinemia (HHcy) is a strong and independent risk factor for cardiovascular disease. HHcy can result from a deficiency in the enzymes or vitamin cofactors required for homocysteine metabolism. Several hypotheses have been proposed to explain the cellular mechanisms by which HHcy promotes cardiovascular disease, including oxidative stress, endoplasmic reticulum (ER) stress and the activation of pro-inflammatory factors. Studies using genetic- and diet-induced animal models of HHcy have now demonstrated a direct causal relationship between HHcy, endothelial dysfunction and accelerated atherosclerosis. These recently established animal models of HHcy provide investigators with important in vivo tools to (i) further understand the cellular mechanisms by which HHcy contributes to endothelial dysfunction and atherosclerosis, and (ii) develop therapeutic agents useful in the treatment of cardiovascular disease.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Aorta / pathology
  • Arteriosclerosis / genetics
  • Arteriosclerosis / metabolism*
  • Arteriosclerosis / pathology
  • Chemokine CCL2 / analysis
  • Chemokine CCL2 / metabolism
  • Diet
  • Endoplasmic Reticulum / metabolism
  • Endothelium, Vascular / metabolism
  • Endothelium, Vascular / pathology
  • Homocysteine / blood
  • Homocysteine / metabolism
  • Homocysteine / urine
  • Humans
  • Hyperhomocysteinemia / genetics
  • Hyperhomocysteinemia / metabolism*
  • Models, Animal
  • Oxidative Stress
  • Risk Factors


  • Chemokine CCL2
  • Homocysteine