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Microvasculopathy-Related Hemorrhagic Tissue Deposition of Iron May Contribute to Fibrosis in Systemic Sclerosis: Hypothesis-Generating Insights from the Literature and Preliminary Findings

Microvascular wall abnormalities demonstrated by nailfold capillaroscopy in systemic sclerosis (SSc) may result in microhemorrhagic deposition of erythrocyte-derived iron. Such abnormalities precede fibrosis, which is orchestrated by myofibroblasts. Iron induces endothelial-to-mesenchymal transition...

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Autores principales: Sfikakis, Petros P., Vlachogiannis, Nikolaos I., Ntouros, Panagiotis A., Mavrogeni, Sophie, Maris, Thomas G., Karantanas, Apostolos H., Souliotis, Vassilis L.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8955192/
https://www.ncbi.nlm.nih.gov/pubmed/35330181
http://dx.doi.org/10.3390/life12030430
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author Sfikakis, Petros P.
Vlachogiannis, Nikolaos I.
Ntouros, Panagiotis A.
Mavrogeni, Sophie
Maris, Thomas G.
Karantanas, Apostolos H.
Souliotis, Vassilis L.
author_facet Sfikakis, Petros P.
Vlachogiannis, Nikolaos I.
Ntouros, Panagiotis A.
Mavrogeni, Sophie
Maris, Thomas G.
Karantanas, Apostolos H.
Souliotis, Vassilis L.
author_sort Sfikakis, Petros P.
collection PubMed
description Microvascular wall abnormalities demonstrated by nailfold capillaroscopy in systemic sclerosis (SSc) may result in microhemorrhagic deposition of erythrocyte-derived iron. Such abnormalities precede fibrosis, which is orchestrated by myofibroblasts. Iron induces endothelial-to-mesenchymal transition in vitro, which is reversed by reactive oxygen species (ROS) scavengers. The conversion of quiescent fibroblasts into profibrotic myofibroblasts has also been associated with ROS-mediated activation of TGF-β1. Given that iron overload predisposes to ROS formation, we hypothesized that the uptake of erythrocyte-derived iron by resident cells promotes fibrosis. Firstly, we show that iron induces oxidative stress in skin-derived and synovial fibroblasts in vitro, as well as in blood mononuclear cells ex vivo. The biological relevance of increased oxidative stress was confirmed by showing the concomitant induction of DNA damage in these cell types. Similar results were obtained in vivo, following intravenous iron administration. Secondly, using magnetic resonance imaging we show an increased iron deposition in the fingers of a patient with early SSc and nailfold microhemorrhages. While a systematic magnetic resonance study to examine tissue iron levels in SSc, including internal organs, is underway, herein we propose that iron may be a pathogenetic link between microvasculopathy and fibrosis and an additional mechanism responsible for increased oxidative stress in SSc.
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spelling pubmed-89551922022-03-26 Microvasculopathy-Related Hemorrhagic Tissue Deposition of Iron May Contribute to Fibrosis in Systemic Sclerosis: Hypothesis-Generating Insights from the Literature and Preliminary Findings Sfikakis, Petros P. Vlachogiannis, Nikolaos I. Ntouros, Panagiotis A. Mavrogeni, Sophie Maris, Thomas G. Karantanas, Apostolos H. Souliotis, Vassilis L. Life (Basel) Communication Microvascular wall abnormalities demonstrated by nailfold capillaroscopy in systemic sclerosis (SSc) may result in microhemorrhagic deposition of erythrocyte-derived iron. Such abnormalities precede fibrosis, which is orchestrated by myofibroblasts. Iron induces endothelial-to-mesenchymal transition in vitro, which is reversed by reactive oxygen species (ROS) scavengers. The conversion of quiescent fibroblasts into profibrotic myofibroblasts has also been associated with ROS-mediated activation of TGF-β1. Given that iron overload predisposes to ROS formation, we hypothesized that the uptake of erythrocyte-derived iron by resident cells promotes fibrosis. Firstly, we show that iron induces oxidative stress in skin-derived and synovial fibroblasts in vitro, as well as in blood mononuclear cells ex vivo. The biological relevance of increased oxidative stress was confirmed by showing the concomitant induction of DNA damage in these cell types. Similar results were obtained in vivo, following intravenous iron administration. Secondly, using magnetic resonance imaging we show an increased iron deposition in the fingers of a patient with early SSc and nailfold microhemorrhages. While a systematic magnetic resonance study to examine tissue iron levels in SSc, including internal organs, is underway, herein we propose that iron may be a pathogenetic link between microvasculopathy and fibrosis and an additional mechanism responsible for increased oxidative stress in SSc. MDPI 2022-03-16 /pmc/articles/PMC8955192/ /pubmed/35330181 http://dx.doi.org/10.3390/life12030430 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Communication
Sfikakis, Petros P.
Vlachogiannis, Nikolaos I.
Ntouros, Panagiotis A.
Mavrogeni, Sophie
Maris, Thomas G.
Karantanas, Apostolos H.
Souliotis, Vassilis L.
Microvasculopathy-Related Hemorrhagic Tissue Deposition of Iron May Contribute to Fibrosis in Systemic Sclerosis: Hypothesis-Generating Insights from the Literature and Preliminary Findings
title Microvasculopathy-Related Hemorrhagic Tissue Deposition of Iron May Contribute to Fibrosis in Systemic Sclerosis: Hypothesis-Generating Insights from the Literature and Preliminary Findings
title_full Microvasculopathy-Related Hemorrhagic Tissue Deposition of Iron May Contribute to Fibrosis in Systemic Sclerosis: Hypothesis-Generating Insights from the Literature and Preliminary Findings
title_fullStr Microvasculopathy-Related Hemorrhagic Tissue Deposition of Iron May Contribute to Fibrosis in Systemic Sclerosis: Hypothesis-Generating Insights from the Literature and Preliminary Findings
title_full_unstemmed Microvasculopathy-Related Hemorrhagic Tissue Deposition of Iron May Contribute to Fibrosis in Systemic Sclerosis: Hypothesis-Generating Insights from the Literature and Preliminary Findings
title_short Microvasculopathy-Related Hemorrhagic Tissue Deposition of Iron May Contribute to Fibrosis in Systemic Sclerosis: Hypothesis-Generating Insights from the Literature and Preliminary Findings
title_sort microvasculopathy-related hemorrhagic tissue deposition of iron may contribute to fibrosis in systemic sclerosis: hypothesis-generating insights from the literature and preliminary findings
topic Communication
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8955192/
https://www.ncbi.nlm.nih.gov/pubmed/35330181
http://dx.doi.org/10.3390/life12030430
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