Early Myocardial Strain Reduction and miR-122-5p Elevation Associated with Interstitial Fibrosis in Anthracycline-Induced Cardiotoxicity

Echocardiographic myocardial strain is crucial for early detection of anthracycline-induced cardiotoxicity, particularly in patients at moderate or high risk. Background/ Objectives: This study investigates changes in global longitudinal strain (GLS) in breast cancer patients with low baseline risk...

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Autores: Caballero Valderrama, María de Regla, Bevilacqua, Elisa, Echevarría Irusta, Miriam, Salvador Bofill, Francisco Javier, Ordóñez Fernández, José Antonio, López Haldón, José Eduardo, Smani Hajami, Tarik, Calderón-Sánchez, Eva M
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2024
País:España
Institución:Universidad de Sevilla (US)
Repositorio:idUS. Depósito de Investigación de la Universidad de Sevilla
OAI Identifier:oai:idus.us.es:11441/174287
Acceso en línea:https://hdl.handle.net/11441/174287
https://doi.org/10.3390/biomedicines13010045
Access Level:acceso abierto
Palabra clave:Cardiotoxicity
Anthracycline
Epirubicin
Global Longitudinal Strain
Circumferential strain
Myocardial fibrosis
Edema
Aquoporin-1
Array
Mir-122-5p
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spelling Early Myocardial Strain Reduction and miR-122-5p Elevation Associated with Interstitial Fibrosis in Anthracycline-Induced CardiotoxicityCaballero Valderrama, María de ReglaBevilacqua, ElisaEchevarría Irusta, MiriamSalvador Bofill, Francisco JavierOrdóñez Fernández, José AntonioLópez Haldón, José EduardoSmani Hajami, TarikCalderón-Sánchez, Eva MCardiotoxicityAnthracyclineEpirubicinGlobal Longitudinal StrainCircumferential strainMyocardial fibrosisEdemaAquoporin-1ArrayMir-122-5pEchocardiographic myocardial strain is crucial for early detection of anthracycline-induced cardiotoxicity, particularly in patients at moderate or high risk. Background/ Objectives: This study investigates changes in global longitudinal strain (GLS) in breast cancer patients with low baseline risk for cardiotoxicity during cancer therapy. We also examined the relationship between echocardiographic strain, structural myocardial changes, and microRNA (miRNA) dysregulation associated with cancer treatment using an animal model. Methods: Echocardiography and blood tests were examined in 33 breast cáncer patients with low baseline risk for cardiotoxicity during anthracycline treatment, with a follow-up at 12 months. Additionally, 16 Wistar rats received epirubicin (20 mg/kg over 4 weeks) to examine cardiac strain and structural changes. Moreover, circulating miRNA levels were assessed in patients’ serum using microarray at the end of the treatment and further analyzed in peripheral blood from the animal model. Results: Pathological GLS values were observed in 27.27% of patients after four cycles, with 15.15% showing reduced left ventricular ejection fraction (LVEF) after 12 months. In the animal model, epirubicin-induced circumferential strain (CS) decrease correlates with myocardial fibrosis assessed histologically and by a significant increase in COL1 and TGFB2 expression. Furthermore, we found a significant decrease in aquaporin1 expression associated with the presence of vacuoles in treated rats. Furthermore, dysregulation in the expression of miRNAs was observed in patients with cardiotoxicity. Among them, hsa-miR-122-5p is increased in both patient and rat serum post-treatment. Conclusions: A notable percentage of low-risk patients exhibited cardiac strain reduction due to cardiotoxicity. Epirubicin treatment caused structural heart changes in rats, highlighting miR-122-5p as a potential fibrosis marker that correlated with echocardiographic parameters.MDPIFisiología Médica y BiofísicaAgencia Estatal de Investigación. EspañaJunta de Andalucía2024info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfapplication/pdfhttps://hdl.handle.net/11441/174287https://doi.org/10.3390/biomedicines13010045reponame:idUS. Depósito de Investigación de la Universidad de Sevillainstname:Universidad de Sevilla (US)InglésBiomedicines, 43 (1).SEC/FEC-INV-BAS 21/030PI-0193-2018PID2022-136279NB-C22https://www.mdpi.com/2227-9059/13/1/45info:eu-repo/semantics/openAccessoai:idus.us.es:11441/1742872026-06-17T12:51:07Z
dc.title.none.fl_str_mv Early Myocardial Strain Reduction and miR-122-5p Elevation Associated with Interstitial Fibrosis in Anthracycline-Induced Cardiotoxicity
title Early Myocardial Strain Reduction and miR-122-5p Elevation Associated with Interstitial Fibrosis in Anthracycline-Induced Cardiotoxicity
spellingShingle Early Myocardial Strain Reduction and miR-122-5p Elevation Associated with Interstitial Fibrosis in Anthracycline-Induced Cardiotoxicity
Caballero Valderrama, María de Regla
Cardiotoxicity
Anthracycline
Epirubicin
Global Longitudinal Strain
Circumferential strain
Myocardial fibrosis
Edema
Aquoporin-1
Array
Mir-122-5p
title_short Early Myocardial Strain Reduction and miR-122-5p Elevation Associated with Interstitial Fibrosis in Anthracycline-Induced Cardiotoxicity
title_full Early Myocardial Strain Reduction and miR-122-5p Elevation Associated with Interstitial Fibrosis in Anthracycline-Induced Cardiotoxicity
title_fullStr Early Myocardial Strain Reduction and miR-122-5p Elevation Associated with Interstitial Fibrosis in Anthracycline-Induced Cardiotoxicity
title_full_unstemmed Early Myocardial Strain Reduction and miR-122-5p Elevation Associated with Interstitial Fibrosis in Anthracycline-Induced Cardiotoxicity
title_sort Early Myocardial Strain Reduction and miR-122-5p Elevation Associated with Interstitial Fibrosis in Anthracycline-Induced Cardiotoxicity
dc.creator.none.fl_str_mv Caballero Valderrama, María de Regla
Bevilacqua, Elisa
Echevarría Irusta, Miriam
Salvador Bofill, Francisco Javier
Ordóñez Fernández, José Antonio
López Haldón, José Eduardo
Smani Hajami, Tarik
Calderón-Sánchez, Eva M
author Caballero Valderrama, María de Regla
author_facet Caballero Valderrama, María de Regla
Bevilacqua, Elisa
Echevarría Irusta, Miriam
Salvador Bofill, Francisco Javier
Ordóñez Fernández, José Antonio
López Haldón, José Eduardo
Smani Hajami, Tarik
Calderón-Sánchez, Eva M
author_role author
author2 Bevilacqua, Elisa
Echevarría Irusta, Miriam
Salvador Bofill, Francisco Javier
Ordóñez Fernández, José Antonio
López Haldón, José Eduardo
Smani Hajami, Tarik
Calderón-Sánchez, Eva M
author2_role author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Fisiología Médica y Biofísica
Agencia Estatal de Investigación. España
Junta de Andalucía
dc.subject.none.fl_str_mv Cardiotoxicity
Anthracycline
Epirubicin
Global Longitudinal Strain
Circumferential strain
Myocardial fibrosis
Edema
Aquoporin-1
Array
Mir-122-5p
topic Cardiotoxicity
Anthracycline
Epirubicin
Global Longitudinal Strain
Circumferential strain
Myocardial fibrosis
Edema
Aquoporin-1
Array
Mir-122-5p
description Echocardiographic myocardial strain is crucial for early detection of anthracycline-induced cardiotoxicity, particularly in patients at moderate or high risk. Background/ Objectives: This study investigates changes in global longitudinal strain (GLS) in breast cancer patients with low baseline risk for cardiotoxicity during cancer therapy. We also examined the relationship between echocardiographic strain, structural myocardial changes, and microRNA (miRNA) dysregulation associated with cancer treatment using an animal model. Methods: Echocardiography and blood tests were examined in 33 breast cáncer patients with low baseline risk for cardiotoxicity during anthracycline treatment, with a follow-up at 12 months. Additionally, 16 Wistar rats received epirubicin (20 mg/kg over 4 weeks) to examine cardiac strain and structural changes. Moreover, circulating miRNA levels were assessed in patients’ serum using microarray at the end of the treatment and further analyzed in peripheral blood from the animal model. Results: Pathological GLS values were observed in 27.27% of patients after four cycles, with 15.15% showing reduced left ventricular ejection fraction (LVEF) after 12 months. In the animal model, epirubicin-induced circumferential strain (CS) decrease correlates with myocardial fibrosis assessed histologically and by a significant increase in COL1 and TGFB2 expression. Furthermore, we found a significant decrease in aquaporin1 expression associated with the presence of vacuoles in treated rats. Furthermore, dysregulation in the expression of miRNAs was observed in patients with cardiotoxicity. Among them, hsa-miR-122-5p is increased in both patient and rat serum post-treatment. Conclusions: A notable percentage of low-risk patients exhibited cardiac strain reduction due to cardiotoxicity. Epirubicin treatment caused structural heart changes in rats, highlighting miR-122-5p as a potential fibrosis marker that correlated with echocardiographic parameters.
publishDate 2024
dc.date.none.fl_str_mv 2024
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/11441/174287
https://doi.org/10.3390/biomedicines13010045
url https://hdl.handle.net/11441/174287
https://doi.org/10.3390/biomedicines13010045
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Biomedicines, 43 (1).
SEC/FEC-INV-BAS 21/030
PI-0193-2018
PID2022-136279NB-C22
https://www.mdpi.com/2227-9059/13/1/45
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv MDPI
publisher.none.fl_str_mv MDPI
dc.source.none.fl_str_mv reponame:idUS. Depósito de Investigación de la Universidad de Sevilla
instname:Universidad de Sevilla (US)
instname_str Universidad de Sevilla (US)
reponame_str idUS. Depósito de Investigación de la Universidad de Sevilla
collection idUS. Depósito de Investigación de la Universidad de Sevilla
repository.name.fl_str_mv
repository.mail.fl_str_mv
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