Systemic Sclerosis (SSc) is a systemic autoimmune disease characterized by progressive fibrosis of skin and multiple internal organs and severe fibroproliferative microvascular alterations. Despite currently available therapeutic approaches SSc has a high mortality rate. The high mortality of SSc is largely caused by severe, progressive and generalized vascular involvement resulting in the development of multiple organ alterations including SSc-associated interstitial lung disease (ILD) and pulmonary arterial hypertension (PAH). These two complications have emerged as the most frequent causes of disability and mortality in SSc.
The pathogenesis of the fibrotic process and the progressive fibroproliferative vasculopathy in SSc is complex and despite extensive investigation the exact mechanisms have remained elusive. Myofibroblasts are the cells ultimately responsible for tissue fibrosis and fibroproliferative vasculopathy in SSc. Tissue myofibroblasts originate from several sources including expansion of quiescent tissue fibroblasts and transmigration and tissue accumulation of circulating CD34+ bone-marrow-derived fibrocytes. Besides these sources, myofibroblasts may result from the phenotypic conversion of epithelial cells, adipocytes or endothelial cells into activated myofibroblasts. The transdifferentiation of endothelial cells into myofibroblasts involves numerous and complex biochemical, molecular, and gene expression events collectively known as endothelial to mesenchymal transition or EndoMT.
Recently, it has been postulated that EndoMT may play a role in the development of tissue fibrosis and SSc-associated ILD and PAH. However, despite the demonstration of the occurrence of EndoMT in experimentally induced cardiac, renal, and pulmonary fibrosis and in several human disorders, the contribution of EndoMT to the pathogenesis of tissue fibrosis and fibroproliferative vasculopathy in SSc has not been generally accepted. Here, the experimental evidence supporting the concept that EndoMT plays a role in the pathogenesis of the vascular alterations in SSc and, more specifically, in the development of SSc-associated ILD and PAH will be critically reviewed.
Disclosure of Interest None declared