Abstract
Microvascular abnormality is a dominant feature of systemic sclerosis. There is increasing evidence that statins, developed as lipid-lowering drugs, yield profound benefits beyond their lipid-lowering effects. These 'pleiotropic' effects suggest that statins may be beneficial for treating SSc vasculopathy. This review focuses on the action of statins on endothelial functions and their potential use in treating SSc. The initial event in the pathogenesis of vascular involvement in SSc has been thought to be endothelial injury, but recent studies have led to another theory--that insufficient vascular repair due to defective vasculogenesis contributes to this process. Statins inhibit cholesterol synthesis, but they also suppress the synthesis of other lipid intermediates, resulting in protection of the endothelium through improvements in endothelial function, mobilization of endothelial precursors, suppression of the inflammatory response, and inhibition of fibrosis. Only a few studies evaluating the clinical benefits of statins have been conducted in SSc patients to date, but one open-label study showed that statins might be effective in improving vascular symptoms. Statins display numerous effects that may be of potential benefit in preventing endothelial dysfunction in SSc patients. Further clinical trials of statins in SSc patients are warranted.