Homocysteine to hydrogen sulfide or hypertension.
Hyperhomocysteinemia, an increased level of plasma homocysteine, is an independent risk factor for the development of premature arterial fibrosis with peripheral and cerebro-vascular, neurogenic and hypertensive heart disease, coronary occlusion and myocardial infarction, as well as venous thromboembolism. It is reported that hyperhomocysteinemia causes vascular dysfunction by two major routes: (1) increasing blood pressure and, (2) impairing the vasorelaxation activity of endothelial-derived nitric oxide. The homocysteine activates metalloproteinases and induces collagen synthesis and causes imbalances of elastin/collagen ratio which compromise vascular elastance. The metabolites from hyperhomocysteinemic endothelium could modify components of the underlying muscle cells, leading to vascular dysfunction and hypertension. Homocysteine metabolizes in the body to produce H(2)S, which is a strong antioxidant and vasorelaxation factor. At an elevated level, homocysteine inactivates proteins by homocysteinylation including its endogenous metabolizing enzyme, cystathionine gamma-lyase. Thus, reduced production of H(2)S during hyperhomocysteinemia exemplifies hypertension and vascular diseases. In light of the present information, this review focuses on the mechanism of hyperhomocysteinemia-associated hypertension and highlights the novel modulatory role of H(2)S to ameliorate hypertension.
Sen
Utpal
U
Department of Physiology & Biophysics, University of Louisville School of Medicine, 500 South Preston Street, Louisville, KY 40202, USA. u0sen001@louisville.edu
Mishra
Paras K
PK
Tyagi
Neetu
N
Tyagi
Suresh C
SC
D002118:Calcium / Q000378:metabolism; D003094:Collagen / Q000378:metabolism; D006710:Homocysteine / Q000097:blood*; D006801:Humans; D006862:Hydrogen Sulfide / Q000378:metabolism*; D020138:Hyperhomocysteinemia / Q000150:complications / Q000378:metabolism; D006973:Hypertension / Q000209:etiology*; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism
D006710:Homocysteine; D009569:Nitric Oxide; D003094:Collagen; D002118:Calcium; D006862:Hydrogen Sulfide
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