Abstract
BackgroundPatients with systemic sclerosis (SSc) are endagered by tissue fibrosis and by microvasculopathy, with the latter caused by endothelial cell expansion/proliferation. SSc-associated fibrosis potentially results from mesenchymal transdifferentiation of endothelial cells. Early Endothelial Progenitor Cells (eEPCs) act proangiogenic under diverse conditions. Aim of the study was to analyze eEPC regeneration and mesenchymal transdifferentiation in patients with limited and diffuse SSs (lSSc and dSSc).MethodsPatients with both, lSSc and dSSc were included into the study. The following parameters were evaluated: eEPC numbers and regeneration, concentrations of vasomodulatory mediators, mesenchymal properties of blood-derived eEPC. Serum samples of healthy subjects and SS patients were used for stimulation of cultured human eEPC, subsequently followed by analysis of mesenchymal cell characteristics and mobility.ResultsTwenty-nine patients were included into the study. Regenerative activity of blood-derived eEPCs did not differ between Controls and patients. Circulating eEPC were significantly lower in all patients with SSc, and in limited and diffuse SSc (lSSc/dSSc). Serum concentrations of promesenchymal TGF-b was elevated in all patients with SSc. Cultured mononuclear cells from SS patients displayed higher abundances of CD31 and of CD31 and aSMA combined. Finally, serum from SSc patients inhibited migration of cultured eEPCs and the cells showed lower sensitivity towards the endothelin antagonist Bosentan.ConclusionsThe eEPC system, which represents an essential element of the endogenous vascular repair machinery is affected in SSc. The increased appearance of mesenchymal properties in eEPC may indicate that alterations of the cells potentially contribute to the accumulation of connective tissue and to vascular malfunction.Electronic supplementary materialThe online version of this article (doi:10.1186/s12891-016-1197-2) contains supplementary material, which is available to authorized users.
Highlights
Patients with systemic sclerosis (SSc) are endagered by tissue fibrosis and by microvasculopathy, with the latter caused by endothelial cell expansion/proliferation
Endothelial Progenitor Cells represent one major subpopulation of EPCs and they have been used for therapeutic purposes in different experimental situations and in humans suffering from ischemic diseases [9,10,11,12,13]
Digital ulcers were diagnosed in three patients with limited systemic sclerosis (lSSc) (14.2 %) and in two subjects (25 %) with diffuse systemic sclerosis (dSSc)
Summary
Patients with systemic sclerosis (SSc) are endagered by tissue fibrosis and by microvasculopathy, with the latter caused by endothelial cell expansion/proliferation. Pathological analysis reveals endothelial cell proliferation in small blood vessels, subsequently leading to vascular obstruction (âonion skin lesionsâ) [2]. Another hallmark in SSc is the Patschan et al BMC Musculoskeletal Disorders (2016) 17:339 endothelial cell proliferation and collagen accumulation are exclusively autoimmune by nature. In 1997, Asahara and colleagues described a population of bloodderived cells, critically involved in neovascularization [5] These cells, termed Endothelial Progenitor Cells (EPCs) are heterogenous in terms of origin and phenotype [6,7,8]. Our particular interest focused on phenotypic characteristics, possibly associated with a pro-mesenchymal switch of the cells within the (peri)vascular microenvironment
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