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Endothelial cell abnormalities and the effects on the surrounding microvasculature is a focal point in the pathogenesis of Systemic Sclerosis disease and may even be the sentinel event for the initiation of this disorder. A better understanding of these processes may improve our understanding of the pathophysiology of Systemic Sclerosis and more specifically the vasculopathy observed. Such knowledge will help us to further current treatments options and design novel therapies for Systemic Sclerosis and other fibrotic disorders.