Targeting mediators of vascular injury in scleroderma.

Increasing evidence suggests that the vasculopathy of scleroderma is mediated by a number of soluble factors and involves a complex interaction between endothelial cells, smooth muscle cells, extracellular matrix, intravascular coagulation factors, and circulating cells. Novel therapeutic approaches beyond vasodilator therapy are being developed by recognizing important molecular pathways involved in scleroderma vascular disease. The success of this strategy is most evident in pulmonary hypertension, an often fatal complication of scleroderma. In this article, the authors explore therapies for scleroderma that target endothelial cells, smooth muscle cells, reactive oxygen species, and circulating blood cells. The authors highlight clinical trials that have investigated the role of prostacyclin (and its analogues) and bosentan in managing scleroderma-related pulmonary hypertension. Finally, the authors look at the potential role of biomarkers as surrogate indicators of active vascular disease in scleroderma.