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2837074 
Journal Article 
Homocysteine Excess and Vascular Endothelium Dysfunction: Delineating the Pathobiological Mechanisms 
Bhatia, P; Gupta, S; Sharma, S 
2014 
Yes 
International Journal of Pharmacology
ISSN: 1811-7775 
10 
4 
200-212 
WOS:000343950200002 
Homocysteine (Hey) excess as a result of impaired metabolism due to deficiency in cofactors (vitamin B-6, B-12, folate) or genetic alteration in metabolic enzymes (Methionine synthase, methyltetrahydrofolate reductase, cystathionine beta-synthase and cystathionine-gamma-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. deigned for these mechanisms may provide novel targets for the development of vascular protective agents. 
Hyperhomocysteinemia; genetic alteration; oxidative stress; phosphatidylinositide 3-kinases; protein kinase B pathway; vascular endothelium dysfunction