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 f...
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2024-12-01
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| author | María de Regla Caballero-Valderrama Elisa Bevilacqua Miriam Echevarría Francisco Javier Salvador-Bofill Antonio Ordóñez José Eduardo López-Haldón Tarik Smani Eva M. Calderón-Sánchez |
| author_facet | María de Regla Caballero-Valderrama Elisa Bevilacqua Miriam Echevarría Francisco Javier Salvador-Bofill Antonio Ordóñez José Eduardo López-Haldón Tarik Smani Eva M. Calderón-Sánchez |
| author_sort | María de Regla Caballero-Valderrama |
| collection | DOAJ |
| 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 cancer 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 <i>COL1</i> and <i>TGFB2</i> 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. |
| format | Article |
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| institution | Kabale University |
| issn | 2227-9059 |
| language | English |
| publishDate | 2024-12-01 |
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| series | Biomedicines |
| spelling | doaj-art-c24e4e021cd74902a6f3f7b241def8b62025-01-24T13:23:49ZengMDPI AGBiomedicines2227-90592024-12-011314510.3390/biomedicines13010045Early Myocardial Strain Reduction and miR-122-5p Elevation Associated with Interstitial Fibrosis in Anthracycline-Induced CardiotoxicityMaría de Regla Caballero-Valderrama0Elisa Bevilacqua1Miriam Echevarría2Francisco Javier Salvador-Bofill3Antonio Ordóñez4José Eduardo López-Haldón5Tarik Smani6Eva M. Calderón-Sánchez7Cardiology Unit, University Hospital Virgen del Rocío, 41013 Seville, SpainCardiovascular Pathophysiology Group, Institute of Biomedicine of Seville-IBiS, University of Seville/Hospital Universitario Virgen de Rocio/CSIC, 41013 Seville, SpainDepartment of Medical Physiology and Biophysics, School of Medicine, University of Seville, 41009 Seville, SpainOncology Unit, University Hospital Virgen del Rocío, 41013 Seville, SpainCardiovascular Pathophysiology Group, Institute of Biomedicine of Seville-IBiS, University of Seville/Hospital Universitario Virgen de Rocio/CSIC, 41013 Seville, SpainCardiology Unit, University Hospital Virgen del Rocío, 41013 Seville, SpainCardiovascular Pathophysiology Group, Institute of Biomedicine of Seville-IBiS, University of Seville/Hospital Universitario Virgen de Rocio/CSIC, 41013 Seville, SpainCardiovascular Pathophysiology Group, Institute of Biomedicine of Seville-IBiS, University of Seville/Hospital Universitario Virgen de Rocio/CSIC, 41013 Seville, SpainEchocardiographic 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 cancer 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 <i>COL1</i> and <i>TGFB2</i> 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.https://www.mdpi.com/2227-9059/13/1/45cardiotoxicityanthracyclineepirubicinglobal longitudinal straincircumferential strainmyocardial fibrosis |
| spellingShingle | María de Regla Caballero-Valderrama Elisa Bevilacqua Miriam Echevarría Francisco Javier Salvador-Bofill Antonio Ordóñez José Eduardo López-Haldón Tarik Smani Eva M. Calderón-Sánchez Early Myocardial Strain Reduction and miR-122-5p Elevation Associated with Interstitial Fibrosis in Anthracycline-Induced Cardiotoxicity Biomedicines cardiotoxicity anthracycline epirubicin global longitudinal strain circumferential strain myocardial fibrosis |
| title | 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_short | 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 |
| topic | cardiotoxicity anthracycline epirubicin global longitudinal strain circumferential strain myocardial fibrosis |
| url | https://www.mdpi.com/2227-9059/13/1/45 |
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