Endothelial cells and endothelial progenitor cells in the pathogenesis of systemic sclerosis

Abstract

Systemic sclerosis (SSc) is a connective tissue disease characterized by excessive fibrosis, microvasculopathy,and autoimmunity. Endothelial cell (EC) injury and subsequent endothelial cell dysfunctionis believed to be an initial event that eventually leads to a vicious pathogenic cycle. This process isfurther enhanced by defective angiogenesis and vasculogenesis, as the vascular repair machinerydoes not work properly. Endothelial progenitor cells (EPCs) are functionally and quantitatively insufficientto recover the endothelium in SSc patients. The dysfunctional ECs and EPCs not only trigger theformation of typical vascular lesions, such as progressive intimal fibrosis in small arteries and the lossof capillaries, but also promote a series of inflammatory and profibrotic processes, such as endothelial-mesenchymal transition and recruitment and accumulation of monocytic EPCs with profibroticproperties. These processes together contribute to the accumulation of extracellular matrix in theaffected tissue. This review features current insights into the roles of ECs and EPCs in the pathogenesisof SSc.