Vascular disease in scleroderma: Mechanisms of vascular injury

Vascular endothelial injury in systemic sclerosis (SSc) includes a spectrum of changes that involve predominantly the microcirculation and arterioles. These changes range from endothelial activation with increased expression of adhesion molecules to capillary necrosis, intimal proliferation of arterioles, and occlusion of blood vessels. The pathologic changes in the blood vessels adversely impact the physiology of many organ systems, with a reduction in the size of microvascular beds leading to decreased organ blood flow and ultimately to a state of chronic ischemia. Current hypotheses in SSc vascular disease suggest a possible chemical or infectious trigger. An enhanced vasoconstrictive tendency in the disease may contribute to the pathogenesis by mechanisms related to ischemia-reperfusion-associated free radical injury. Activation of cellular and humoral immunity may lead to vascular injury through the production of autoantibodies and the release of products of activated T cells that can directly damage the endothelium. A variety of circulating markers reflecting the degree of vascular injury have been described, including plasma von Willebrand factor, certain cytokines, and soluble adhesion molecules. The working hypothesis in the pathogeneses of SSc vascular disease is shown in (Fig. 1).