In-stent restenosis is associated with proliferative skin healing and specific immune and endothelial cell profiles: results from the RACHEL trial

Introduction: In-stent restenosis (ISR) is a major challenge in interventional cardiology. Both ISR and excessive skin healing are aberrant hyperplasic responses, which may be functionally related. However, the cellular component underlying ISR remains unclear, especially regarding vascular homeosta...

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Autores: Lozano, Í., Bangueses, R., Rodríguez, I., Pevida, M., Rodríguez-Aguilar, R., Rodríguez, D., Espasandin Arias, Martina, Llames, S., Meana, Á., Suárez, A., Rodríguez-Carrio, J.
Tipo de recurso: artículo
Fecha de publicación:2023
País:España
Institución:Servizo Galego de Saúde (SERGAS)
Repositorio:RUNA. Repositorio da Consellería de Sanidade e Sergas
OAI Identifier:oai:runa.sergas.gal:20.500.11940/21624
Acceso en línea:https://portalcientifico.sergas.gal//documentos/64ab356d4eb9d841a6e5c0d7
http://hdl.handle.net/20.500.11940/21624
Access Level:acceso abierto
Palabra clave:Humans
Endothelial Cells
Coronary Restenosis
Stents
Phenotype
AS Pontevedra
CHUP
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spelling In-stent restenosis is associated with proliferative skin healing and specific immune and endothelial cell profiles: results from the RACHEL trialLozano, Í.Bangueses, R.Rodríguez, I.Pevida, M.Rodríguez-Aguilar, R.Rodríguez, D.Espasandin Arias, MartinaLlames, S.Meana, Á.Suárez, A.Rodríguez-Carrio, J.HumansEndothelial CellsCoronary RestenosisStentsPhenotypeAS PontevedraCHUPIntroduction: In-stent restenosis (ISR) is a major challenge in interventional cardiology. Both ISR and excessive skin healing are aberrant hyperplasic responses, which may be functionally related. However, the cellular component underlying ISR remains unclear, especially regarding vascular homeostasis. Recent evidence suggest that novel immune cell populations may be involved in vascular repair and damage, but their role in ISR has not been explored. The aims of this study is to analyze (i) the association between ISR and skin healing outcomes, and (ii) the alterations in vascular homeostasis mediators in ISR in univariate and integrative analyses. Methods: 30 patients with ?1 previous stent implantation with restenosis and 30 patients with ?1 stent without restenosis both confirmed in a second angiogram were recruited. Cellular mediators were quantified in peripheral blood by flow cytometry. Skin healing outcomes were analyzed after two consecutive biopsies. Results: Hypertrophic skin healing was more frequent in ISR patients (36.7%) compared to those ISR-free (16.7%). Patients with ISR were more likely to develop hypertrophic skin healing patterns (OR 4.334 [95% CI 1.044-18.073], p=0.033), even after correcting for confounders. ISR was associated with decreased circulating angiogenic T-cells (p=0.005) and endothelial progenitor cells (p<0.001), whereas CD4+CD28null and detached endothelial cells counts were higher (p<0.0001 and p=0.006, respectively) compared to their ISR-free counterparts. No differences in the frequency of monocyte subsets were found, although Angiotensin-Converting Enzyme expression was increased (non-classical: p<0.001; and intermediate: p<0.0001) in ISR. Despite no differences were noted in Low-Density Granulocytes, a relative increase in the CD16- compartment was observed in ISR (p=0.004). An unsupervised cluster analysis revealed the presence of three profiles with different clinical severity, unrelated to stent types or traditional risk factors. Conclusion: ISR is linked to excessive skin healing and profound alterations in cellular populations related to vascular repair and endothelial damage. Distinct cellular profiles can be distinguished within ISR, suggesting that different alterations may uncover different ISR clinical phenotypes.This work was supported by European Union FEDER funds, Fondo de Investigacion Sanitaria (grant references PI18/01293 and PI21/00054) and the Intramural Program from Instituto de Investigacion Sanitaria del Principado de Asturias (ISPA) (grant reference ISPA Emergentes JRC). IR is financially supported by Fundacion para la Investigacion y la Innovacion Biosanitaria del Principado de Asturias (FINBA).2023info:eu-repo/semantics/articlehttps://portalcientifico.sergas.gal//documentos/64ab356d4eb9d841a6e5c0d7http://hdl.handle.net/20.500.11940/21624reponame:RUNA. Repositorio da Consellería de Sanidade e Sergasinstname:Servizo Galego de Saúde (SERGAS)Ingléshttp://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:runa.sergas.gal:20.500.11940/216242026-06-12T08:40:47Z
dc.title.none.fl_str_mv In-stent restenosis is associated with proliferative skin healing and specific immune and endothelial cell profiles: results from the RACHEL trial
title In-stent restenosis is associated with proliferative skin healing and specific immune and endothelial cell profiles: results from the RACHEL trial
spellingShingle In-stent restenosis is associated with proliferative skin healing and specific immune and endothelial cell profiles: results from the RACHEL trial
Lozano, Í.
Humans
Endothelial Cells
Coronary Restenosis
Stents
Phenotype
AS Pontevedra
CHUP
title_short In-stent restenosis is associated with proliferative skin healing and specific immune and endothelial cell profiles: results from the RACHEL trial
title_full In-stent restenosis is associated with proliferative skin healing and specific immune and endothelial cell profiles: results from the RACHEL trial
title_fullStr In-stent restenosis is associated with proliferative skin healing and specific immune and endothelial cell profiles: results from the RACHEL trial
title_full_unstemmed In-stent restenosis is associated with proliferative skin healing and specific immune and endothelial cell profiles: results from the RACHEL trial
title_sort In-stent restenosis is associated with proliferative skin healing and specific immune and endothelial cell profiles: results from the RACHEL trial
dc.creator.none.fl_str_mv Lozano, Í.
Bangueses, R.
Rodríguez, I.
Pevida, M.
Rodríguez-Aguilar, R.
Rodríguez, D.
Espasandin Arias, Martina
Llames, S.
Meana, Á.
Suárez, A.
Rodríguez-Carrio, J.
author Lozano, Í.
author_facet Lozano, Í.
Bangueses, R.
Rodríguez, I.
Pevida, M.
Rodríguez-Aguilar, R.
Rodríguez, D.
Espasandin Arias, Martina
Llames, S.
Meana, Á.
Suárez, A.
Rodríguez-Carrio, J.
author_role author
author2 Bangueses, R.
Rodríguez, I.
Pevida, M.
Rodríguez-Aguilar, R.
Rodríguez, D.
Espasandin Arias, Martina
Llames, S.
Meana, Á.
Suárez, A.
Rodríguez-Carrio, J.
author2_role author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Humans
Endothelial Cells
Coronary Restenosis
Stents
Phenotype
AS Pontevedra
CHUP
topic Humans
Endothelial Cells
Coronary Restenosis
Stents
Phenotype
AS Pontevedra
CHUP
description Introduction: In-stent restenosis (ISR) is a major challenge in interventional cardiology. Both ISR and excessive skin healing are aberrant hyperplasic responses, which may be functionally related. However, the cellular component underlying ISR remains unclear, especially regarding vascular homeostasis. Recent evidence suggest that novel immune cell populations may be involved in vascular repair and damage, but their role in ISR has not been explored. The aims of this study is to analyze (i) the association between ISR and skin healing outcomes, and (ii) the alterations in vascular homeostasis mediators in ISR in univariate and integrative analyses. Methods: 30 patients with ?1 previous stent implantation with restenosis and 30 patients with ?1 stent without restenosis both confirmed in a second angiogram were recruited. Cellular mediators were quantified in peripheral blood by flow cytometry. Skin healing outcomes were analyzed after two consecutive biopsies. Results: Hypertrophic skin healing was more frequent in ISR patients (36.7%) compared to those ISR-free (16.7%). Patients with ISR were more likely to develop hypertrophic skin healing patterns (OR 4.334 [95% CI 1.044-18.073], p=0.033), even after correcting for confounders. ISR was associated with decreased circulating angiogenic T-cells (p=0.005) and endothelial progenitor cells (p<0.001), whereas CD4+CD28null and detached endothelial cells counts were higher (p<0.0001 and p=0.006, respectively) compared to their ISR-free counterparts. No differences in the frequency of monocyte subsets were found, although Angiotensin-Converting Enzyme expression was increased (non-classical: p<0.001; and intermediate: p<0.0001) in ISR. Despite no differences were noted in Low-Density Granulocytes, a relative increase in the CD16- compartment was observed in ISR (p=0.004). An unsupervised cluster analysis revealed the presence of three profiles with different clinical severity, unrelated to stent types or traditional risk factors. Conclusion: ISR is linked to excessive skin healing and profound alterations in cellular populations related to vascular repair and endothelial damage. Distinct cellular profiles can be distinguished within ISR, suggesting that different alterations may uncover different ISR clinical phenotypes.
publishDate 2023
dc.date.none.fl_str_mv 2023
dc.type.none.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv https://portalcientifico.sergas.gal//documentos/64ab356d4eb9d841a6e5c0d7
http://hdl.handle.net/20.500.11940/21624
url https://portalcientifico.sergas.gal//documentos/64ab356d4eb9d841a6e5c0d7
http://hdl.handle.net/20.500.11940/21624
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.rights.none.fl_str_mv http://creativecommons.org/licenses/by/4.0/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv http://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv openAccess
dc.source.none.fl_str_mv reponame:RUNA. Repositorio da Consellería de Sanidade e Sergas
instname:Servizo Galego de Saúde (SERGAS)
instname_str Servizo Galego de Saúde (SERGAS)
reponame_str RUNA. Repositorio da Consellería de Sanidade e Sergas
collection RUNA. Repositorio da Consellería de Sanidade e Sergas
repository.name.fl_str_mv
repository.mail.fl_str_mv
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