Autologous hematopoietic stem cell transplantation modifies specific aspects of systemic sclerosis-related microvasculopathy
Objective: Autologous hematopoietic stem cell transplantation (AHSCT) is a therapeutic option for patients with severe and progressive systemic sclerosis (SSc). Here, we aimed to investigate how AHSCT affects the vasculopathy of SSc patients. Methods: Twenty-seven SSc patients were retrospectively a...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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SAGE Publishing
2022-03-01
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| Series: | Therapeutic Advances in Musculoskeletal Disease |
| Online Access: | https://doi.org/10.1177/1759720X221084845 |
| _version_ | 1811311825756618752 |
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| author | Maynara Santana-Gonçalves Djúlio Zanin-Silva Álvaro Henrique-Neto Daniela A. Moraes Marianna Y. Kawashima- Vasconcelos João R. Lima-Júnior Juliana B. E. Dias Vinícius Bragagnollo Júlia T. C. de Azevedo Dimas T. Covas Kelen C. R. Malmegrim Leandra Ramalho Maria Carolina Oliveira |
| author_facet | Maynara Santana-Gonçalves Djúlio Zanin-Silva Álvaro Henrique-Neto Daniela A. Moraes Marianna Y. Kawashima- Vasconcelos João R. Lima-Júnior Juliana B. E. Dias Vinícius Bragagnollo Júlia T. C. de Azevedo Dimas T. Covas Kelen C. R. Malmegrim Leandra Ramalho Maria Carolina Oliveira |
| author_sort | Maynara Santana-Gonçalves |
| collection | DOAJ |
| description | Objective: Autologous hematopoietic stem cell transplantation (AHSCT) is a therapeutic option for patients with severe and progressive systemic sclerosis (SSc). Here, we aimed to investigate how AHSCT affects the vasculopathy of SSc patients. Methods: Twenty-seven SSc patients were retrospectively assessed, before and after AHSCT, for vessel morphology (nailfold capillaroscopy), skin expression of endothelial markers and serum levels of markers of inflammation, angiogenesis and endothelial activation. Skin biopsies were analyzed by immunohistochemistry (IHC) for expression of CD31, VE-cadherin, E-selectin, angiopoietin-1 (Ang1), angiopoietin-2 (Ang2), Tie-2, vascular endothelial growth factor A (VEGFA), vascular endothelial growth factor receptor 2 (VEGFR2), and endothelin-1 before and 12 months post-AHSCT. Serum samples from SSc patients were assessed before and up to 36 months after AHSCT for IL-6, von Willebrand factor (vWF), CXC Motif Chemokine Ligand 8 (CXCL8), Endothelin-1, epidermal growth factor (EGF), VEGFA, Pentraxin-3, Intercellular Adhesion Molecule 1 (ICAM-1), E-selectin, P-selectin, Thrombomodulin and IL-18 levels, and compared to healthy control samples. Results: On nailfold capillaroscopy, the number of capillaries increased at 1 year, while giant capillaries decreased at 6 months and 1 year after AHSCT. In the skin biopsies, expression of E-selectin notably decreased and Ang1 increased after AHSCT. At baseline, all vascular markers evaluated in the serum were significantly higher in SSc patients when compared to healthy controls, except for ICAM-1. When compared at different time points after AHSCT, Thrombomodulin, Pentraxin-3, vWF, and IL-18 levels remained generally stable at high levels until 36 months after AHSCT. Conclusion: Our results suggest that AHSCT contributes to improvements of the vessel morphology and dermal microvasculopathy, but does not normalize elevated levels of serum vascular markers in SSc patients. Additional vascular therapeutic approaches might contribute to more effectively treat the endothelial injury. |
| first_indexed | 2024-04-13T10:24:38Z |
| format | Article |
| id | doaj.art-fe689f9799d147c78acb120702099a53 |
| institution | Directory Open Access Journal |
| issn | 1759-7218 |
| language | English |
| last_indexed | 2024-04-13T10:24:38Z |
| publishDate | 2022-03-01 |
| publisher | SAGE Publishing |
| record_format | Article |
| series | Therapeutic Advances in Musculoskeletal Disease |
| spelling | doaj.art-fe689f9799d147c78acb120702099a532022-12-22T02:50:21ZengSAGE PublishingTherapeutic Advances in Musculoskeletal Disease1759-72182022-03-011410.1177/1759720X221084845Autologous hematopoietic stem cell transplantation modifies specific aspects of systemic sclerosis-related microvasculopathyMaynara Santana-GonçalvesDjúlio Zanin-SilvaÁlvaro Henrique-NetoDaniela A. MoraesMarianna Y. Kawashima- VasconcelosJoão R. Lima-JúniorJuliana B. E. DiasVinícius BragagnolloJúlia T. C. de AzevedoDimas T. CovasKelen C. R. MalmegrimLeandra RamalhoMaria Carolina OliveiraObjective: Autologous hematopoietic stem cell transplantation (AHSCT) is a therapeutic option for patients with severe and progressive systemic sclerosis (SSc). Here, we aimed to investigate how AHSCT affects the vasculopathy of SSc patients. Methods: Twenty-seven SSc patients were retrospectively assessed, before and after AHSCT, for vessel morphology (nailfold capillaroscopy), skin expression of endothelial markers and serum levels of markers of inflammation, angiogenesis and endothelial activation. Skin biopsies were analyzed by immunohistochemistry (IHC) for expression of CD31, VE-cadherin, E-selectin, angiopoietin-1 (Ang1), angiopoietin-2 (Ang2), Tie-2, vascular endothelial growth factor A (VEGFA), vascular endothelial growth factor receptor 2 (VEGFR2), and endothelin-1 before and 12 months post-AHSCT. Serum samples from SSc patients were assessed before and up to 36 months after AHSCT for IL-6, von Willebrand factor (vWF), CXC Motif Chemokine Ligand 8 (CXCL8), Endothelin-1, epidermal growth factor (EGF), VEGFA, Pentraxin-3, Intercellular Adhesion Molecule 1 (ICAM-1), E-selectin, P-selectin, Thrombomodulin and IL-18 levels, and compared to healthy control samples. Results: On nailfold capillaroscopy, the number of capillaries increased at 1 year, while giant capillaries decreased at 6 months and 1 year after AHSCT. In the skin biopsies, expression of E-selectin notably decreased and Ang1 increased after AHSCT. At baseline, all vascular markers evaluated in the serum were significantly higher in SSc patients when compared to healthy controls, except for ICAM-1. When compared at different time points after AHSCT, Thrombomodulin, Pentraxin-3, vWF, and IL-18 levels remained generally stable at high levels until 36 months after AHSCT. Conclusion: Our results suggest that AHSCT contributes to improvements of the vessel morphology and dermal microvasculopathy, but does not normalize elevated levels of serum vascular markers in SSc patients. Additional vascular therapeutic approaches might contribute to more effectively treat the endothelial injury.https://doi.org/10.1177/1759720X221084845 |
| spellingShingle | Maynara Santana-Gonçalves Djúlio Zanin-Silva Álvaro Henrique-Neto Daniela A. Moraes Marianna Y. Kawashima- Vasconcelos João R. Lima-Júnior Juliana B. E. Dias Vinícius Bragagnollo Júlia T. C. de Azevedo Dimas T. Covas Kelen C. R. Malmegrim Leandra Ramalho Maria Carolina Oliveira Autologous hematopoietic stem cell transplantation modifies specific aspects of systemic sclerosis-related microvasculopathy Therapeutic Advances in Musculoskeletal Disease |
| title | Autologous hematopoietic stem cell transplantation modifies specific aspects of systemic sclerosis-related microvasculopathy |
| title_full | Autologous hematopoietic stem cell transplantation modifies specific aspects of systemic sclerosis-related microvasculopathy |
| title_fullStr | Autologous hematopoietic stem cell transplantation modifies specific aspects of systemic sclerosis-related microvasculopathy |
| title_full_unstemmed | Autologous hematopoietic stem cell transplantation modifies specific aspects of systemic sclerosis-related microvasculopathy |
| title_short | Autologous hematopoietic stem cell transplantation modifies specific aspects of systemic sclerosis-related microvasculopathy |
| title_sort | autologous hematopoietic stem cell transplantation modifies specific aspects of systemic sclerosis related microvasculopathy |
| url | https://doi.org/10.1177/1759720X221084845 |
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