In-stent restenosis is associated with proliferative skin healing and specific immune and endothelial cell profiles: results from the RACHEL trial
IntroductionIn-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 homeostasi...
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Frontiers Media S.A.
2023-05-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1138247/full |
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| author | Íñigo Lozano Íñigo Lozano Roi Bangueses Isabel Rodríguez Marta Pevida Marta Pevida Marta Pevida Raúl Rodríguez-Aguilar Diana Rodríguez Martina Espasandín-Arias Sara Llames Sara Llames Sara Llames Sara Llames Álvaro Meana Álvaro Meana Álvaro Meana Ana Suárez Ana Suárez Javier Rodríguez-Carrio Javier Rodríguez-Carrio |
| author_facet | Íñigo Lozano Íñigo Lozano Roi Bangueses Isabel Rodríguez Marta Pevida Marta Pevida Marta Pevida Raúl Rodríguez-Aguilar Diana Rodríguez Martina Espasandín-Arias Sara Llames Sara Llames Sara Llames Sara Llames Álvaro Meana Álvaro Meana Álvaro Meana Ana Suárez Ana Suárez Javier Rodríguez-Carrio Javier Rodríguez-Carrio |
| author_sort | Íñigo Lozano |
| collection | DOAJ |
| description | IntroductionIn-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.Methods30 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.ResultsHypertrophic 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.ConclusionISR 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. |
| first_indexed | 2024-03-13T08:20:24Z |
| format | Article |
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| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-03-13T08:20:24Z |
| publishDate | 2023-05-01 |
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| series | Frontiers in Immunology |
| spelling | doaj.art-24210e6e02c44c00978215714655d77a2023-05-31T09:21:13ZengFrontiers Media S.A.Frontiers in Immunology1664-32242023-05-011410.3389/fimmu.2023.11382471138247In-stent restenosis is associated with proliferative skin healing and specific immune and endothelial cell profiles: results from the RACHEL trialÍñigo Lozano0Íñigo Lozano1Roi Bangueses2Isabel Rodríguez3Marta Pevida4Marta Pevida5Marta Pevida6Raúl Rodríguez-Aguilar7Diana Rodríguez8Martina Espasandín-Arias9Sara Llames10Sara Llames11Sara Llames12Sara Llames13Álvaro Meana14Álvaro Meana15Álvaro Meana16Ana Suárez17Ana Suárez18Javier Rodríguez-Carrio19Javier Rodríguez-Carrio20Department of Cardiology, Hospital Universitario Cabueñes, Gijón, Asturias, SpainCardiac Pathology Research Group, Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), Oviedo, Asturias, SpainDepartment of Cardiology, Hospital Universitario Cabueñes, Gijón, Asturias, SpainCardiac Pathology Research Group, Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), Oviedo, Asturias, SpainBlood Tansfusion Center and Tissue Bank of Asturias, Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Oviedo, Asturias, SpainGrupo de Investigación en Oftalmología, Ciencias de la Visión y Terapias Avanzadas (GOVITA), Instituto de Salud del Principado de Asturias (ISPA), Oviedo, Asturias, SpainInstituto Universitario Fernández-Vega, Fundación de Investigación Oftalmológica, Oviedo, Asturias, SpainDepartment of Pathology Anatomy, Hospital Universitario Cabueñes, Gijón, Asturias, SpainDepartment of Pathology Anatomy, Hospital Universitario Cabueñes, Gijón, Asturias, SpainDepartment of Dermatology, Hospital Universitario Cabueñes, Gijón, Asturias, SpainBlood Tansfusion Center and Tissue Bank of Asturias, Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Oviedo, Asturias, SpainGrupo de Investigación en Oftalmología, Ciencias de la Visión y Terapias Avanzadas (GOVITA), Instituto de Salud del Principado de Asturias (ISPA), Oviedo, Asturias, SpainCentro de Investigación Biomédica en Red en Enfermedades Raras (CIBERER), Instituto de Salud Carlos III, Madrid, SpainFundación Jiménez Díaz, Madrid, SpainBlood Tansfusion Center and Tissue Bank of Asturias, Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Oviedo, Asturias, SpainGrupo de Investigación en Oftalmología, Ciencias de la Visión y Terapias Avanzadas (GOVITA), Instituto de Salud del Principado de Asturias (ISPA), Oviedo, Asturias, SpainInstituto Universitario Fernández-Vega, Fundación de Investigación Oftalmológica, Oviedo, Asturias, Spain0Area of Immunology, Department of Functional Biology, University of Oviedo, Oviedo, Asturias, Spain1Grupo de Investigación Básica y Traslacional en Enfermedades Inflamatorias, Instituto de Investigación Sanitaria del Principado de Asturias, Oviedo, Asturias, Spain0Area of Immunology, Department of Functional Biology, University of Oviedo, Oviedo, Asturias, Spain1Grupo de Investigación Básica y Traslacional en Enfermedades Inflamatorias, Instituto de Investigación Sanitaria del Principado de Asturias, Oviedo, Asturias, SpainIntroductionIn-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.Methods30 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.ResultsHypertrophic 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.ConclusionISR 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.https://www.frontiersin.org/articles/10.3389/fimmu.2023.1138247/fullneoatherosclerosisvascular biologyinflammationskin healingrestenosisT cells |
| spellingShingle | Íñigo Lozano Íñigo Lozano Roi Bangueses Isabel Rodríguez Marta Pevida Marta Pevida Marta Pevida Raúl Rodríguez-Aguilar Diana Rodríguez Martina Espasandín-Arias Sara Llames Sara Llames Sara Llames Sara Llames Álvaro Meana Álvaro Meana Álvaro Meana Ana Suárez Ana Suárez Javier Rodríguez-Carrio Javier Rodríguez-Carrio In-stent restenosis is associated with proliferative skin healing and specific immune and endothelial cell profiles: results from the RACHEL trial Frontiers in Immunology neoatherosclerosis vascular biology inflammation skin healing restenosis T cells |
| title | 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_short | 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 |
| topic | neoatherosclerosis vascular biology inflammation skin healing restenosis T cells |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1138247/full |
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