Is scleroderma a vasculopathy?

Described as an autoimmune collagen vascular disease, the most striking feature of scleroderma may be a systemic vasculopathy. This vasculopathy includes characteristic noninflammatory macrovascular and microvascular changes with dramatic and possibly occlusive formation of a thickened neointima. Scleroderma vessels also have an unusual endothelial phenotype, with loss of normal markers including vascular endothelial (VE)-cadherin. These endothelial cells express type 1 interferon and regulator of G protein signaling 5 (RGS5), two molecules associated with vascular rarefaction. These genes may be important because tissue is hypoxic with high levels of vascular endothelial growth factor (VEGF), especially early in the disease. The combination of VEGF and rarefaction is not necessarily paradoxical. VEGF-mediated angiogenesis creates labile vessels that may not survive unless the vessel acquires a smooth muscle coat. The combination of interferon and RGS5 is consistent with an antiangiogenic phenotype. We offer a hypothesis that places vascular injury at the center of this disease and also suggest possible clinical approaches for arresting and/or reversing the disease.

The pathology of scleroderma vascular disease.

Systemic sclerosis is characterized by three distinct pathologic processes: fibrosis, cellular/humoral autoimmunity, and specific vascular changes. Although a mild vasculitis may sometimes be present, the vascular pathology of scleroderma is not necessarily inflammatory and is best characterized as a vasculopathy. In this article, the authors propose that SSc vasculopathy is the result of an early event involving vascular injury that eventuates in a vicious cycle mediated in part by the immune process. The subsequent vascular malformation and rarefaction may be a function of systemic angiogenic dysregulation, with over expression of vascular endothelial growth factor but a lack of proper interactions with smooth muscle cells needed to stabilize and organize blood vessels.