Homocysteine Excess and Vascular Endothelium Dysfunction: Delineating the Pathobiological Mechanisms

Review Article

Homocysteine Excess and Vascular Endothelium Dysfunction: Delineating the Pathobiological Mechanisms

Pankaj Bhatia, Sushma Gupta and Saurabh Sharma

Homocysteine (Hcy) excess as a result of impaired metabolism due to deficiency in cofactors (vitamin B₆, B₁₂, folate) or genetic alteration in metabolic enzymes (Methionine synthase, methyltetrahydrofolate reductase, cystathionine β-synthase and cystathionine-γ-lyase) lead to acquired metabolic anomaly known as hyperhomocysteinemia. Hyperhomocysteinemia (HHcy) is an independent major casual determinant of cerebrovascular and cardiovascular disorders viz., carotid artery disease, atherosclerosis, stroke and vascular dementia. The intense dysfunction of vascular endothelium following hyperhomocysteinemia has been implicated as a factor in the extension of pathological conditions. One of the therapeutic goals of modern vascular biology is to design strategies to limit vascular endothelium dysfunction. A sound understanding of the abnormality in homocysteine metabolic pathway and vascular endothelium dysfunction is necessary before a specific intervention is pursued. Summarized is the description of the homocysteine, its fate and abnormalities that leads to hyperhomocysteinemia. Further, the pathobiology of homocysteine excess which are noted to cause oxidative stress, impairment of intracellular transduction pathways, release of inflammatory mediators, dysfunction of endothelial progenitor cells and RBCs hemolysis is also discussed. Collectively these pathobiological mechanisms causes the decrease in cell survival, activation of proinflammatory mediators, apoptosis and consequently leads to vascular endothelium dysfunction. On the basis of the multiple toxic effects of homocysteine excess, interventions designed for these mechanisms may provide novel targets for the development of vascular protective agents.

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Pankaj Bhatia, Sushma Gupta and Saurabh Sharma, 2014. Homocysteine Excess and Vascular Endothelium Dysfunction: Delineating the Pathobiological Mechanisms. International Journal of Pharmacology, 10: 200-212.

DOI: 10.3923/ijp.2014.200.212

URL: https://scialert.net/abstract/?doi=ijp.2014.200.212

International Journal of Pharmacology

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Pankaj Bhatia

Sushma Gupta

Saurabh Sharma

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Review Article

Homocysteine Excess and Vascular Endothelium Dysfunction: Delineating the Pathobiological Mechanisms

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