gms | German Medical Science

Background: In inflammatory myopathies (IIM) vascular pathology includes depositions of complement in the case of necrotizing myopathy (NM) and dermatomyositis (DM). The latter is a humoral-mediated vasculopathy characterized by capillary reduction and destruction. In polymyositis (PM) CD8+ cytotoxic T cells can be detected in the muscle and the vascular system. Recent studies confirmed the assumption of an endothelial dysfunction in IIM. In addition our studies showed a vascular upregulation of CXCR6, a chemokine receptor recruiting EPCs, in muscle biopsies. Therefore angiogenic mediators became of interest as endothelial progenitor cells (EPCs) are required for neovascularization upon ischemic damage and can be recruited by angiogenic mediators through biological effects. Aim of this project was to analyze the presence and alterations of CXCL16 as the only chemokine of CXCR6 as well as of VEGF and Angiopoetin 1 in NM, DM and PM.

Methods: Thirty-four patients (DM 17, PM 10, NM 7) and 40 healthy controls were included into the study. The following EPC-related parameters were evaluated: blood-derived EPC colonies (culture assay) and peripheral circulating EPCs (CD133+/VEGFR2+ cells-cytometric analysis). Plasma-related parameters were evaluated from thirty patients (DM 14, PM 10, NM 6) via enzyme-linked immunosorbent assay to indicate the amount of CXCL16, VEGF and Angiopoetin 1. Muscle biopsies were available from 22 patients (DM 10, PM 6, NM 6). Cryosections from muscle biopsies were stained for CD31 (endothelium), CXCR6 (T-lymphocyte receptor for tissue recruitment), Nestin (regeneration of mature endothelial cells) and MHC (inflammation) and evaluated by immunofluorescence followed by manual multi-parameter assessment.

Results: Blood-derived EPC colonies were significantly lower in NM, DM and PM as compared to healthy controls. Staining of muscle biopsies revealed strong signals for vascular CXCR6 in DM, NM and PM. The number of capillaries counted via CD31 was significantly reduced in the DM and PM group. The marker of inflammation (MHC-I) and the marker of regeneration (Nestin) were significantly correlated in DM, PM and less intense in NM. Angiogenic mediators showed significantly strong signals for CXCL16 in all IIM – correlating to the strong signals of vascular CXCR6 in muscle biopsies. This effect could not be demonstrated for VEGF and Angiopoetin 1.

Conclusion: The data suggest that (I) impairement of the EPC system may perpetuate vascular damage in DM / PM / NM. (II) Higher abundances of vascular CXCR6 and blood derived CXCL16 suggest EPC recruitment. (III) Nevertheless there is a significant capillary reduction seen in the DM and PM group. Therefore the angiogenic effect of CXCL16 has to be proved.