The Role of Vascular Endothelial Growth Factor in Systemic Sclerosis

Abstract

The pathological hallmarks of Systemic Sclerosis (SSc) constitute an inter-related triad of autoimmunity, vasculopathy and tissue remodeling. Many signaling mediators have been implicated in SSc pathology; most focusing on individual components of this pathogenic triad and current treatment paradigms tend to approach management of such as distinct entities. The present review shall examine the role of Vascular Endothelial Growth Factor (VEGF) in SSc pathogenesis. We shall outline potential mechanisms whereby differential Vascular Endothelial Growth Factor-A (VEGF-A) isoform expression (through conventional and alternative VEGF-A splicing,) may influence the relevant burden of vasculopathy and fibrosis offering novel insight into clinical heterogeneity and disease progression in SSc. Emerging therapeutic approaches targeting VEGF signaling pathways might play an important role in the management of SSc, and differential VEGF-A splice isoform expression may provide a tool for personalized medicine approaches to disease management.

Keywords: Systemic sclerosis (scleroderma); VEGF-A; VEGF-A165b; anti-angiogenic; fibrosis; pathogenesis; pro-fibrotic; vascular endothelial growth factor; vasculopathy..