Figure 1.

Roles of ECs and EPCs in pathogenesis of SSc.

A variety of triggers damage the endothelium, leading to subsequent expression of a series of pro-angiogenic factors, growth factors, and chemokines. Increased levels of these mediators promote recruitment of conventional EPCs from bone marrow, however, the vascular repair machinery is intrinsically impaired, which results in altered EC functions that induce the activation of fibroblasts by a direct interaction and their trans-differentiation into myofibroblasts via Endo-MT. Additionally, in compensation for the insufficient vascular repair process, monocytic EPCs with M2 features are recruited into circulation and are made to accumulate at the affected sites, thereby promoting ECM deposition and tissue fibrosis.

ECs: endothelial cells; vSMCs: vascular smooth muscle cells; EPCs: endothelial progenitor cells; VEGF: vascular endothelial growth factor; FGF-2: basic fibroblast growth factor-2; MCP-1: monocyte chemoattractant protein-1; SDF-1: stromal-derived factor-1; MMP12: matrix metalloproteinase 12; TGF-β: transforming growth factor β; ECM: extracellular matrix.