Impact of Hyperhomocyst(e)inemia on Endothelial Function

Author(s): Agostino Virdis, Lorenzo Ghiadoni, Stefania Pinto, Daniele Versari, Guido Salvetti, Stefano Taddei, Antonio Salvetti.

Journal Name: Vascular Disease Prevention

Volume 1 , Issue 2 , 2004

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Abstract:

Homocysteine is a sulfur-containing intermediate aminoacid, produced by the metabolism of methionine. Circulating homocysteine can be increased by a genetic deficiency of enzymatic pathways involved in its catabolism as well as by environmental factors including nutritional deficiencies, life style factors or physiological conditions, which mainly induce deficiency of folate, vitamin B12 and vitamin B6. Homocysteine exerts a prothrombotic and proatherosclerotic effect, mainly caused by a direct deleterious effect on the endothelium. An early event of this interaction is endothelial dysfunction, characterised by a reduced nitric oxide (NO) availability due to an abnormal production of reactive oxygen species induced by homocysteine. This alteration has been confirmed in humans, either in conditions of acute or fasting chronic hyperhomocysteinaemia. When hyperhomocysteinaemia is associated with another cardiovascular risk factor such as hypertension, a further reduction of endothelial function occurs: an effect likely due to an exacerbated production of oxidative stress. Folates also exert beneficial effects on endothelial function by mechanisms independent of changes in plasma homocysteine levels, including an effect on free homocysteine, an antioxidant effect or an action on endothelial NO synthase (eNOS). Although the deleterious effect exerted by hyperhomocysteinemia on endothelial function is well recognised, its role in the pathogenesis of atherosclerotic lesions or cardiovascular events is still to be established. Finally, although available evidence suggests that hyperhomocysteinaemia could be an independent predictor of recurrent cardiovascular events, the possibility that a reduction in plasma homocysteine induced by vitamin therapy can diminish the risk of cardiovascular events is still under evaluation.

Keywords: endothelium, homocysteine, antioxidant

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Article Details

VOLUME: 1
ISSUE: 2
Year: 2004
Page: [87 - 99]
Pages: 13
DOI: 10.2174/1567270010401020087
Price: $58

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