AUTHOR=Lemmer D. , Schmidt J. , Kummer K. , Lemmer B. , Wrede A. , Seitz C. , Balcarek P. , Schwarze K. , Müller G. A. , Patschan D. , Patschan S. 

TITLE=Impairment of muscular endothelial cell regeneration in dermatomyositis

JOURNAL=Frontiers in Neurology

VOLUME=Volume 13 - 2022

YEAR=2022

URL=https://www.frontiersin.org/journals/neurology/articles/10.3389/fneur.2022.952699

DOI=10.3389/fneur.2022.952699

ISSN=1664-2295

ABSTRACT=Background and aim
Inflammatory myopathies is a group of heterogeneous subsets in terms of etiology, (immuno)pathology, and clinical findings. Endothelial cell injury, as it occurs in DM is a common fea-ture of numerous inflammatory and non-inflammatory vascular diseases. Vascular regeneration is mediated by both, local and blood-derived mechanisms such as the mobilization and activation of so-called proangiogenic cells (PACs) or early Endothelial Progenitor cells (eEPCs). The current study aimed to evaluate parameters of eEPC integrity in dermatomyositis (DM), com-pared to necrotitzing myopathy (NM) and to non-myopathic controls.
Methods
Blood samples from DM and NM patients were compared to non-myopathic controls and analyzed for the following parameters: circulating CD133+/VEGFR-2+ cells, number of Colony-Forming Unit Endothelial Cells (CFU-ECs), concentrations of Angiopoietin 1, Vascular Endothelial Growth Factor (VEGF) and CXCL-16. Muscle biopsies from DM and NM subjects underwent immunofluorescence analysis for CXCR6, Nestin, and CD31 (PECAM-1). Finally, myotubes, derived from healthy donors were stimulated with serum samples from DM and NM patients, subsequently followed by RT-PCR for the following candidates: IL-1, IL-6, Nestin, and CD31. 
Results
Seventeen (17) DM patients, 7 NM patients and 40 non-myopathic controls were included. CD133+/VEGFR-2+ cells did not differ between the groups. Both, DM and NM patients showed lower CFU-ECs than controls. In DM, intramuscular CD31 abundances were significantly reduced, which indicated vascular rarefaction. Muscular CXCR6 was elevated in both diseases. Circulating CXCL-16 was higher in DM and NM in contrast, compared to controls. Serum from patients with DM but not NM induced a profound upregulation of mRNS expression of CD31 and IL-6 in cultured myotubes.
Conclusions
Our study demonstrates the loss of intramuscular microvessels in DM, accompanied by endo-thelial activation in DM and NM. Vascular regeneration was impaired in DM and NM. The findings suggest a role for inflammation-associated vascular damage in the pathogenesis of DM.