Evidence for endothelial‐to‐mesenchymal transition in human brain arteriovenous malformations
| Autor: | Aaron K. McCormick, Breanna M. Allen, Steven D. Chang, Lorelei D. Shoemaker |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Pathology medicine.medical_specialty Cell Medicine (miscellaneous) 03 medical and health sciences 0302 clinical medicine medicine endothelial‐to‐mesenchymal transition (EndMT) Research Articles arteriovenous malformation (AVM) lcsh:R5-920 biology Mesenchymal stem cell Human brain myofibroblast cerebrovascular disease SNAI2 030104 developmental biology medicine.anatomical_structure KLF4 030220 oncology & carcinogenesis SNAI1 biology.protein Molecular Medicine ACTA2 lcsh:Medicine (General) Myofibroblast Research Article |
| Zdroj: | Clinical and Translational Medicine Clinical and Translational Medicine, Vol 10, Iss 2, Pp n/a-n/a (2020) |
| ISSN: | 2001-1326 |
| Popis: | Background Brain arteriovenous malformations (AVMs) are rare, potentially devastating cerebrovascular lesions that can occur in both children and adults. AVMs are largely sporadic and the basic disease biology remains unclear, limiting advances in both detection and treatment. This study aimed to investigate human brain AVMs for endothelial‐to‐mesenchymal transition (EndMT), a process recently implicated in cerebral cavernous malformations (CCMs). Methods We used 29 paraffin‐embedded and 13 fresh/frozen human brain AVM samples to profile expression of panels of EndMT‐associated proteins and RNAs. CCMs, a cerebrovascular disease also characterized by abnormal vasculature, were used as a primary comparison, given that EndMT specifically contributes to CCM disease biology. AVM‐derived cell lines were isolated from three fresh, surgical AVM samples and characterized by protein expression. Results We observed high collagen deposition, high PAI‐1 expression, and expression of EndMT‐associated transcription factors such as KLF4, SNAI1, and SNAI2 and mesenchymal‐associated markers such as VIM, ACTA2, and S100A4. SMAD‐dependent TGF‐β signaling was not strongly activated in AVMs and this pathway may be only partially involved in mediating EndMT. Using serum‐free culture conditions, we isolated myofibroblast‐like cell populations from AVMs that expressed a unique range of proteins associated with mature cell types and with EndMT. Conditioned medium from these cells led to increased proliferation of HUVECs and SMCs. Conclusions Collectively, our results suggest a role for EndMT in AVM disease. This may lead to new avenues for disease models to further our understanding of disease mechanisms, and to the development of improved diagnostics and therapeutics. |
| Databáze: | OpenAIRE |
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