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Angiogenic T cell expansion correlates with severity of peripheral vascular damage in systemic sclerosis

studies are required to clarify the function of Tang cells and investigate the mechanisms responsible for their change in SSc. Author Contributions Conceptualization: Mirko Manetti, Sara Pratesi, Enrico ... Maggi, Marco Matucci-Cerinic. Data curation: Mirko Manetti, Sara Pratesi, Eloisa Romano, Irene Rosa, Lidia Ibba-Manneschi, Marco Matucci-Cerinic. Formal analysis: Mirko Manetti, Sara Pratesi, Eloisa

The crowded crossroad to angiogenesis in systemic sclerosis: where is the key to the problem?

In systemic sclerosis (SSc), peripheral vasculopathy is characterized by a progressive and irreversible loss of capillaries following endothelial cell injury, due to defects in both vascular repair and expected increase in new vessel growth (angiogenesis). The discovery of key molecular targets may help to develop the most effective therapeutic strategy for the SSc-related ...

Proangiogenic effects of soluble α-Klotho on systemic sclerosis dermal microvascular endothelial cells

Background Systemic sclerosis (SSc) is characterized by endothelial cell (EC) apoptosis, impaired angiogenesis and peripheral microvasculopathy. Soluble α-Klotho (sKl) is a pleiotropic molecule with multiple effects on ECs, including antioxidant and vasculoprotective activities. On the EC surface, sKl interacts with vascular endothelial growth factor (VEGF) receptor-2 (VEGFR-2) and ...

Systemic Sclerosis Sera Impair Angiogenic Performance of Dermal Microvascular Endothelial Cells: Therapeutic Implications of Cyclophosphamide

In systemic sclerosis (SSc), dermal capillaries are progressively lost with consequent chronic tissue hypoxia insufficiently compensated by angiogenesis. Clinical studies reported that intravenous cyclophosphamide (CYC) may improve SSc-related peripheral microvascular damage. Recently, we showed that CYC treatment may normalize SSc sera-induced abnormalities in endothelial ...

Plexin-D1/Semaphorin 3E pathway may contribute to dysregulation of vascular tone control and defective angiogenesis in systemic sclerosis

Introduction The vascular and nervous systems have several anatomic and molecular mechanism similarities. Emerging evidence suggests that proteins involved in transmitting axonal guidance cues, including members of class III semaphorin (Sema3) family, play a critical role in blood vessel guidance during physiological and pathological vascular development. Sema3E is a natural ...

Decreased expression of the endothelial cell-derived factor EGFL7 in systemic sclerosis: potential contribution to impaired angiogenesis and vasculogenesis

Introduction Microvascular damage and defective angiogenesis and vasculogenesis have a major role in the pathogenesis of systemic sclerosis (SSc). Epidermal growth factor-like domain 7 (EGFL7) is a proangiogenic molecule which is predominantly expressed and secreted by endothelial cells and their progenitors and controls vascular development and integrity. In this study, we ...

Systemic sclerosis sera affect fibrillin-1 deposition by dermal blood microvascular endothelial cells: therapeutic implications of cyclophosphamide

Introduction Systemic sclerosis (SSc) is a connective tissue disorder characterized by endothelial cell injury, autoimmunity and fibrosis. The following three fibrillin-1 alterations have been reported in SSc. (1) Fibrillin-1 microfibrils are disorganized in SSc dermis. (2) Fibrillin-1 microfibrils produced by SSc fibroblasts are unstable. (3) Mutations in the FBN1 gene and ...