The role of vascular endothelium in fibroblast activation and tissue fibrosis, particularly in scleroderma (systemic sclerosis) and pachydermoperiostosis (primary hypertrophic osteoarthropathy).

The vascular endothelium is an organ that is distinguished by its versatility and ability to modulate its surroundings. Endothelial cells (EC) interact with a variety of cell types including fibroblasts (FB), smooth muscle cells, circulating mononuclear cells, platelets and other cell types. This paper will focus on the interaction between endothelial cells and fibroblasts in the process of fibrosis. Vascular changes are described in most human fibrotic models, i.e. radiation, bleomycin, wound healing and particularly in scleroderma. FB migration to the perivascular spaces and proliferation is seen in the early settings of tissue fibrosis. The role of EC in this process is not precisely known; however, the EC contribution to fibrosis is likely to be multifactorial and may involve a spectrum of delicate mechanisms and an array of chemical signals. The induction of FB chemotaxis and FB proliferation by the EC's release of chemotactic factors and mitogens is one possible pathway of FB activation. Another major mechanism involves EC mobilization, guidance and regulation of mononuclear cell infiltration in the perivascular spaces and the subsequent impact of that process on FB activation. Histologic studies of human fibrotic disorders have emphasized early FB proliferation. The role of EC in the induction of FB proliferation should be evaluated carefully in order to understand human fibrosis.