The Pathology of Scleroderma Vascular Disease

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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.

Section snippets

Vascular pathology of scleroderma

The functional changes in the vasculature of patients with SSc are well described by others [17]. The most prominent of these changes is Raynaud's phenomenon, a widespread form of vasospasm that is prodromal or concurrent with other changes in SSc. The focus of this article is on understanding the morphologic changes using current knowledge of vascular biology.

A hypothesis

These data provide the first objective evidence for loss of vessels in SSc, and show that the rarefaction associated with SSc is reversible. Coordinate changes in expression of three molecules already implicated in angiogenesis or antiangiogenesis suggest that control of expression of these three molecules may be part of the underlying mechanism for at least the vascular component of this disease. Because rarefaction has been little studied, these data may have implications for other diseases

Summary

SSc is a poorly understood connective tissue disease with a characteristic vasculopathy. This vasculopathy has two key features: first, a concentric and often progressively occlusive intimal hyperplasia; and second, a pattern of microvascular injury with an “antiangiogenic phenotype,” characteristic gene expression, malformation and rarefaction. In a preliminary study, the authors found that these vascular changes are reversible with autologous transplant of stem cells and high dose

Acknowledgments

The authors would like to acknowledge the following people who assisted with this manuscript: Simon Corrie, Jeremy Fleming, Richard Nash, David K. Pritchard, Joshua Aaron Sonnen, and Jinnan Wang. We especially wish to thank the patients who enabled us to obtain biopsy material and the Scelroderma Research Foundation for stimulating and supporting this work.

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    Funding support was provided by the Scleroderma Research Foundation. Dr. Fleming is a fellow of the Scleroderma Research Foundation.

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