The Pathology of Scleroderma Vascular Disease
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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Cited by (59)
Change of the microvascularization in systemic sclerosis, a matter of air
2021, Best Practice and Research: Clinical RheumatologyCitation Excerpt :Although the pathogenesis of SSc is not completely clear, the understanding of the factors contributing to the development and progression of the disease is increasing. Vasculopathy is one of the primary processes that characterize SSc and is present early in the disease [16–18]. The two other key processes are inflammation and fibrosis.
Chemical exposure-induced systemic fibrosing disorders: Novel insights into systemic sclerosis etiology and pathogenesis
2020, Seminars in Arthritis and RheumatismCitation Excerpt :However, it was not until Campbell and LeRoy postulated the hypothesis that vascular alterations played a crucial role in the global pathogenesis of SSc [165] that a large number of studies were initiated to examine the essential involvement of vascular abnormalities in SSc including the exaggerated and persistent activation of cells mediating the fibrotic process. The role of vascular alterations in the development of the SSc pathologic manifestations has been subsequently explored in a large number of publications [Reviewed in 166-172]. More recently, the focus of investigation has been shifted to emphasize that alterations in EC are at the center of SSc pathogenesis [173-178].
Imbalanced serum levels of Ang1, Ang2 and VEGF in systemic sclerosis: Integrated effects on microvascular reactivity
2019, Microvascular ResearchCitation Excerpt :Vascular alterations in SSc predominantly affect the microvasculature and are primarily due to endothelial cells (ECs) injury (activation/apoptosis) resulting from perivascular immune and inflammatory reaction. It leads to loss of endothelium integrity with ECs detachment and in consequence to deformations of microvessels with significant enlargement of the capillaries followed by capillary collapse and rarefaction (Altorok et al., 2014; Cutolo and Sulli, 2015; Fleming and Schwartz, 2008; Freemont et al., 1992; Kahaleh, 2008; Manetti et al., 2010; Matucci-Cerinic et al., 2017). These specific sequential abnormalities in microcirculation are reflected by nailfold videocapillaroscopy (NVC) morphological changes in form of enlarged loops/giants, capillary crush with microhaemorrhages and capillary loss (Cutolo et al., 2004, 2013, 2018; Ghizzoni et al., 2015; Smith et al., 2016a, 2016b).
Granulocytes: Neutrophils, basophils, eosinophils
2019, The Autoimmune Diseases
Funding support was provided by the Scleroderma Research Foundation. Dr. Fleming is a fellow of the Scleroderma Research Foundation.