Vaskuläres Regenerationspotential im Muskel und endotheliale Vorläuferzellen im Blut bei Patienten mit Myositis

Vascular Regeneration Potential in Muscle and Endothelial Progenitor Cells in Blood of Patients with Myositis

by Dana Lemmer
Doctoral thesis
Date of Examination:2018-06-06
Date of issue:2018-05-28
Advisor:PD Dr. Susann Patschan
Referee:PD Dr. Susann Patschan
Referee:Prof. Dr. Jens Schmidt
Persistent Address: http://dx.doi.org/10.53846/goediss-6861

 

 

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Abstract

English

The pathogenesis of dermatomyositis (DM) is believed to rely on humeral mechanisms, whereas the hypothesized cause of polymyositis (PM) are cytotoxic T cells. Necrotizing myopathy (NM) is histopathologically characterized by necrosis of muscle fibres in absence of inflammation. Vascular pathology includes depositions of complement in the case of NM and DM. The latter is characterized by capillary reduction and destruction. Aim of this project was to analyse the presence and functional alteration of early Endothelial Progenitor Cells (eEPCs) in blood and of relevant markers in muscle biopsies in DM, PM and NM. Blood-derived eEPC colonies were significantly lower in NM, DM and PM as compared to healthy controls. Percentages of peripheral circulating eEPCs (CD133+/VEGFR-2+) showed a lowering tendency in DM and PM. 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. Angiogenic mediators showed significantly strong signals for CXCL16 in all myopathies. The data suggest that (I) vascular damage and eEPC mechanisms are involved in all three types of myositis. (II) Higher abundances of vascular CXCR6 and blood derived CXCL16 suggest eEPC recruitment. (III) These data contribute to a better understanding of the pathogenesis of idiopathic inflammatory myopathies (IIM). 
Keywords: myositis; endothelial progenitor cells; EPCs; idiopathic inflammatory myopathy; dermatomyositis; polymyositis; necrotizing myopathy
 
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