Endothelial dysfunction in systemic sclerosis.

Abstract

Microvascular endothelial cells (MVECs) injury is a critical early event in the pathogenesis of systemic sclerosis (SSc). We aim to provide the reader with an update regarding the role of MVECs in the pathogenesis of SSc and the mechanisms for MVECs dysfunction in the disease. Recent evidence confirms the central role for MVECs in the pathogenesis of SSc, and suggests further mechanisms for MVECs injury. The impact of MVECs perturbations in SSc goes beyond the initiation of the vascular disease to include activation of fibroblasts through the release of cytokines and growth factors like connective tissue growth factor that induce an active and aggressive form of fibroblasts. Moreover, recent studies highlighted a more prominent role for epigenetic factors in the pathogenesis of SSc, and suggested defects in the function of progenitor endothelial cells in SSc. Recent reports helped to shed light on the role of antiendothelial cell antibodies in the pathogenesis of SSc, especially purified subsets of these antibodies like anti-ICAM-1 antibodies, and also reported possible mechanisms for defective vascular endothelial growth factor signaling. It is clear that MVECs dysfunction is a key element in the pathogenesis of SSc, but the initial triggers for MVEC dysfunction remain uncharacterized.