| Summary: | endothelium plays a key role in the pathophysiology of vascular disease. Oxidative stress plays a significant role in the progression of vascular disease. Homocysteine is a non-proteinogenic amino acid derived from methionine and is now established as an independent risk factor for vascular disease. Vitamin B12 and folate are established therapeutic agents used to ameliorate homocysteine indu~ed damage.. The clarification ofprecise oxidative stress regulated signalling pathways and their relationship with the regulation ofHsps, vascular gene expression and endothelial dysfunction, represents an important paradigm for understanding the pathogenesis ofvascular disease and should infonn future therapeutic strategies primarily associated ·with the benefits ofantioxidant therapy. Growing evidence supports the notion that oxidative damage to proteins is becoming a unifying mechanism of several risk factors associated with vascular disease.The work presented in this thesis aims to characterise the molecular mechanisms by which Hsps may be regulated in response to various stressors. Furthennore, the involvement of Hsps in the protection ofvascular endothelial cells from oxidative stress will be analysed. This work will also evaluate the potential benefit from novel thiolatocobalamins CGSCbl and NACCbl). Investigations have been carried out on various EC cell lines using cell culture methods and reporting assays. In addition, genetic reportmg methods have been used to assess the effect of gene silencing undertaken by chemical and RNAi protocols. The effects of antioxidant treatments were evaluated as potential therapeutic agents.
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