Hyperhomocyst(e)inemia is associated with an increased risk for atherosclerotic disease and venous thromboembolism. The impact of elevated plasma homocysteine levels seems to be clinically relevant, since the total cardiovascular risk of hyperhomocyst(e)inemia is comparable to the risk associated with hyperlipidemia or smoking. There is substantial evidence for impairment of endothelial function in human and animal models of atherosclerosis, occurring even before development of overt plaques. interestingly endothelial dysfunction appears to be a sensitive indicator of the process of atherosclerotic lesion development and predicts future vascular events. NO is the most potent endogenous vasodilator known. It is released by the endothelium, and reduced NO bioavailability is responsible for impaired endothelium-dependent vasorelaxation in hyperhomocyst(e)inemia and other metabolic disorders associated with vascular disease. Substances leading to impaired endothelial function as a consequence of reduced NO generation are endogenous NO synthase inhibitors such as ADMA. Indeed there is accumulating evidence from animal and human studies that ADMA, endothelial function and homocyst(e)ine might be closely interrelated. Specifically elevations of ADMA associated with impaired endothelium-dependent relaxation were found in chronic hyperhomocyst(e)inemia, as well as after acute elevation of plasma homocyst(e)ine following oral methionine intake. The postulated mechanisms for ADMA accumulation are increased methylation of arginine residues within proteins, as well as reduced metabolism of ADMA by the enzyme DDAH, but they still need to be confirmed to be operative in vivo. Hyperhomocyst(e)inemia, as well as subsequent endothelial dysfunction can be successfully treated by application of folate and B vitamins. Since ADMA seems to play a central role in homocyst(e)ine-induced endothelial dysfunction, another way of preventing vascular disease in patients with elevated homocyst(e)ine concentrations could be supplementation with L-arginine to reverse the detrimental effects of ADMA.
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Taipei Vet Gen Hosp, Dept Med, Div Gen Med, Taipei 11217, Taiwan
Natl Yang Ming Univ, Dept Med, Sch Med, Taipei 112, TaiwanTaipei Vet Gen Hosp, Dept Med, Div Gastroenterol, Taipei 11217, Taiwan
Yang, Ying-Ying
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Lee, Tzung-Yan
Huang, Yi-Tsau
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Natl Yang Ming Univ, Sch Med, Inst Tradit Med, Taipei 112, TaiwanTaipei Vet Gen Hosp, Dept Med, Div Gastroenterol, Taipei 11217, Taiwan
Huang, Yi-Tsau
Chan, Che-Chang
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Taipei Vet Gen Hosp, Dept Med, Div Gastroenterol, Taipei 11217, Taiwan
Natl Yang Ming Univ, Dept Med, Sch Med, Taipei 112, TaiwanTaipei Vet Gen Hosp, Dept Med, Div Gastroenterol, Taipei 11217, Taiwan
Chan, Che-Chang
Yeh, Yi-Chen
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Natl Yang Ming Univ, Dept Med, Sch Med, Taipei 112, Taiwan
Taipei Vet Gen Hosp, Dept Pathol, Taipei 11217, TaiwanTaipei Vet Gen Hosp, Dept Med, Div Gastroenterol, Taipei 11217, Taiwan
Yeh, Yi-Chen
Lee, Fa-Yauh
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Taipei Vet Gen Hosp, Dept Med, Div Gastroenterol, Taipei 11217, TaiwanTaipei Vet Gen Hosp, Dept Med, Div Gastroenterol, Taipei 11217, Taiwan
Lee, Fa-Yauh
Lee, Shou-Dong
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Taipei Vet Gen Hosp, Dept Med, Div Gastroenterol, Taipei 11217, TaiwanTaipei Vet Gen Hosp, Dept Med, Div Gastroenterol, Taipei 11217, Taiwan
Lee, Shou-Dong
Lin, Han-Chieh
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Taipei Vet Gen Hosp, Dept Med, Div Gastroenterol, Taipei 11217, Taiwan
Natl Yang Ming Univ, Dept Med, Sch Med, Taipei 112, TaiwanTaipei Vet Gen Hosp, Dept Med, Div Gastroenterol, Taipei 11217, Taiwan