Is scleroderma a vasculopathy?

Abstract

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.

ABCG2pos lung mesenchymal stem cells are a novel pericyte subpopulation that contributes to fibrotic remodeling

“…It is considered a marker of rare pericytes (10), and its expression is typically not detected in adult lung (72). Its expression has been associated with vascular remodeling, rarefaction, or loss of microvessels and regulation of vascular tone (21,35,36,74). Periostin is a profibrotic and proinflammatory protein hypothesized to be a potential biomarker in IPF (68,93).…”

Shared Gene Expression Patterns in Mesenchymal Progenitors Derived from Lung and Epidermis in Pulmonary Arterial Hypertension: Identifying Key Pathways in Pulmonary Vascular Disease

“…Microvascular pathology in both lung and skin is also present in systemic sclerosis, which suggests that the skin-derived MCs may share similar gene signatures with lung MPCs and therefore may be exploited to identify changes in the pulmonary vascular bed as well as tissuespecific patterns of protein expression. 4,[33][34][35][36] In order to identify whether the selected gene expression patterns identified were recapitulated in skin MCs, we analyzed gene expression of human skin FBs. Cells were isolated from 5 groups: controls, patients with known BMPR2 mutations but not PAH, patients with known BMPR2 mutations and PAH, patients with IPAH, and patients with CAV1 mutations and PAH.…”

Association of TIMP-1 +372 SNP with digital ulcer manifestation in female systemic sclerosis patients

“…Digital ulcers, expression of the ischemic vasculopathy, are characterized by arterial intimal hyperplasia with fibrosis [3,4]. Vascular network, known to be critically dependent on the interaction with extracellular matrix [5], displays an irregular architecture in SSc patients [6].…”