Abstract
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 H2S, which is a strong antioxidant and vasorelaxation factor. At an elevated level, homocysteine inactivates proteins by homocysteinylation including its endogenous metabolizing enzyme, cystathionine γ-lyase. Thus, reduced production of H2S 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 H2S to ameliorate hypertension.
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Abbreviations
- AT1:
-
Angiotensin type 1
- CBS:
-
Cystathionine-β synthase
- CSE:
-
Cystathionine-γ lyase
- CTGF:
-
Connective tissue growth factor
- ECM:
-
Extracellular matrix
- H2S:
-
Hydrogen sulfide
- MMP:
-
Matrix metalloproteinase
- NO:
-
Nitric oxide
- NOS:
-
Nitric oxide synthase
- O ●−2 :
-
Superoxide
- ROS:
-
Reactive oxygen species
- TIMP:
-
Tissue inhibitor of metalloproteinase
- VSMC:
-
Vascular smooth muscle cell
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Acknowledgments
This research was supported, in part, by the National Institutes of Health grants, HL-74185, HL-71010, HL-88012 and NS-51568.
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Sen, U., Mishra, P.K., Tyagi, N. et al. Homocysteine to Hydrogen Sulfide or Hypertension. Cell Biochem Biophys 57, 49–58 (2010). https://doi.org/10.1007/s12013-010-9079-y
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DOI: https://doi.org/10.1007/s12013-010-9079-y