Mitochondrial Oxidative Stress Promotes Cardiac Remodeling in Myocardial Infarction through the Activation of Endoplasmic Reticulum Stress
We have evaluated cardiac function and fibrosis in infarcted male Wistar rats treated with MitoQ (50 mg/kg/day) or vehicle for 4 weeks. A cohort of patients admitted with a first episode of acute MI were also analyzed with cardiac magnetic resonance and T1 mapping during admission and at a 12-month...
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MDPI AG
2022-06-01
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Series: | Antioxidants |
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Online Access: | https://www.mdpi.com/2076-3921/11/7/1232 |
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author | Francisco V. Souza-Neto Fabian Islas Sara Jiménez-González María Luaces Bunty Ramchandani Ana Romero-Miranda Beatriz Delgado-Valero Elena Roldan-Molina Melchor Saiz-Pardo Mª Ángeles Cerón-Nieto Luis Ortega-Medina Ernesto Martínez-Martínez Victoria Cachofeiro |
author_facet | Francisco V. Souza-Neto Fabian Islas Sara Jiménez-González María Luaces Bunty Ramchandani Ana Romero-Miranda Beatriz Delgado-Valero Elena Roldan-Molina Melchor Saiz-Pardo Mª Ángeles Cerón-Nieto Luis Ortega-Medina Ernesto Martínez-Martínez Victoria Cachofeiro |
author_sort | Francisco V. Souza-Neto |
collection | DOAJ |
description | We have evaluated cardiac function and fibrosis in infarcted male Wistar rats treated with MitoQ (50 mg/kg/day) or vehicle for 4 weeks. A cohort of patients admitted with a first episode of acute MI were also analyzed with cardiac magnetic resonance and T1 mapping during admission and at a 12-month follow-up. Infarcted animals presented cardiac hypertrophy and a reduction in the left ventricular ejection fraction (LVEF) and E- and A-waves (E/A) ratio when compared to controls. Myocardial infarction (MI) rats also showed cardiac fibrosis and endoplasmic reticulum (ER) stress activation. Binding immunoglobulin protein (BiP) levels, a marker of ER stress, were correlated with collagen I levels. MitoQ reduced oxidative stress and prevented all these changes without affecting the infarct size. The LVEF and E/A ratio in patients with MI were 57.6 ± 7.9% and 0.96 ± 0.34, respectively. No major changes in cardiac function, extracellular volume fraction (ECV), or LV mass were observed at follow-up. Interestingly, the myeloperoxidase (MPO) levels were associated with the ECV in basal conditions. BiP staining and collagen content were also higher in cardiac samples from autopsies of patients who had suffered an MI than in those who had died from other causes. These results show the interactions between mitochondrial oxidative stress and ER stress, which can result in the development of diffuse fibrosis in the context of MI. |
first_indexed | 2024-03-09T12:20:09Z |
format | Article |
id | doaj.art-bf2bd02cc2d54a4c8eec2c54fc090496 |
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issn | 2076-3921 |
language | English |
last_indexed | 2024-03-09T12:20:09Z |
publishDate | 2022-06-01 |
publisher | MDPI AG |
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series | Antioxidants |
spelling | doaj.art-bf2bd02cc2d54a4c8eec2c54fc0904962023-11-30T22:41:54ZengMDPI AGAntioxidants2076-39212022-06-01117123210.3390/antiox11071232Mitochondrial Oxidative Stress Promotes Cardiac Remodeling in Myocardial Infarction through the Activation of Endoplasmic Reticulum StressFrancisco V. Souza-Neto0Fabian Islas1Sara Jiménez-González2María Luaces3Bunty Ramchandani4Ana Romero-Miranda5Beatriz Delgado-Valero6Elena Roldan-Molina7Melchor Saiz-Pardo8Mª Ángeles Cerón-Nieto9Luis Ortega-Medina10Ernesto Martínez-Martínez11Victoria Cachofeiro12Departamento de Fisiología, Facultad de Medicina, Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Universidad Complutense de Madrid, 28040 Madrid, SpainServicio de Cardiología, Instituto Cardiovascular, Hospital Clínico San Carlos, 28040 Madrid, SpainDepartamento de Fisiología, Facultad de Medicina, Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Universidad Complutense de Madrid, 28040 Madrid, SpainServicio de Cardiología, Instituto Cardiovascular, Hospital Clínico San Carlos, 28040 Madrid, SpainServicio de Cirugía Cardiaca Infantil, Hospital La Paz, 28046 Madrid, SpainDepartamento de Fisiología, Facultad de Medicina, Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Universidad Complutense de Madrid, 28040 Madrid, SpainDepartamento de Fisiología, Facultad de Medicina, Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Universidad Complutense de Madrid, 28040 Madrid, SpainBiobanco del Hospital Clínico San Carlos, Instituto de Investigación de Salud del Hospital Clínico San Carlos, 28040 Madrid, SpainDepartamento de Patología, Hospital Clínico San Carlos, 28040 Madrid, SpainDepartamento de Patología, Hospital Clínico San Carlos, 28040 Madrid, SpainBiobanco del Hospital Clínico San Carlos, Instituto de Investigación de Salud del Hospital Clínico San Carlos, 28040 Madrid, SpainDepartamento de Fisiología, Facultad de Medicina, Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Universidad Complutense de Madrid, 28040 Madrid, SpainDepartamento de Fisiología, Facultad de Medicina, Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Universidad Complutense de Madrid, 28040 Madrid, SpainWe have evaluated cardiac function and fibrosis in infarcted male Wistar rats treated with MitoQ (50 mg/kg/day) or vehicle for 4 weeks. A cohort of patients admitted with a first episode of acute MI were also analyzed with cardiac magnetic resonance and T1 mapping during admission and at a 12-month follow-up. Infarcted animals presented cardiac hypertrophy and a reduction in the left ventricular ejection fraction (LVEF) and E- and A-waves (E/A) ratio when compared to controls. Myocardial infarction (MI) rats also showed cardiac fibrosis and endoplasmic reticulum (ER) stress activation. Binding immunoglobulin protein (BiP) levels, a marker of ER stress, were correlated with collagen I levels. MitoQ reduced oxidative stress and prevented all these changes without affecting the infarct size. The LVEF and E/A ratio in patients with MI were 57.6 ± 7.9% and 0.96 ± 0.34, respectively. No major changes in cardiac function, extracellular volume fraction (ECV), or LV mass were observed at follow-up. Interestingly, the myeloperoxidase (MPO) levels were associated with the ECV in basal conditions. BiP staining and collagen content were also higher in cardiac samples from autopsies of patients who had suffered an MI than in those who had died from other causes. These results show the interactions between mitochondrial oxidative stress and ER stress, which can result in the development of diffuse fibrosis in the context of MI.https://www.mdpi.com/2076-3921/11/7/1232cardiac fibrosismitochondrial oxidative stressendoplasmic reticulum stressmyocardial ischemia |
spellingShingle | Francisco V. Souza-Neto Fabian Islas Sara Jiménez-González María Luaces Bunty Ramchandani Ana Romero-Miranda Beatriz Delgado-Valero Elena Roldan-Molina Melchor Saiz-Pardo Mª Ángeles Cerón-Nieto Luis Ortega-Medina Ernesto Martínez-Martínez Victoria Cachofeiro Mitochondrial Oxidative Stress Promotes Cardiac Remodeling in Myocardial Infarction through the Activation of Endoplasmic Reticulum Stress Antioxidants cardiac fibrosis mitochondrial oxidative stress endoplasmic reticulum stress myocardial ischemia |
title | Mitochondrial Oxidative Stress Promotes Cardiac Remodeling in Myocardial Infarction through the Activation of Endoplasmic Reticulum Stress |
title_full | Mitochondrial Oxidative Stress Promotes Cardiac Remodeling in Myocardial Infarction through the Activation of Endoplasmic Reticulum Stress |
title_fullStr | Mitochondrial Oxidative Stress Promotes Cardiac Remodeling in Myocardial Infarction through the Activation of Endoplasmic Reticulum Stress |
title_full_unstemmed | Mitochondrial Oxidative Stress Promotes Cardiac Remodeling in Myocardial Infarction through the Activation of Endoplasmic Reticulum Stress |
title_short | Mitochondrial Oxidative Stress Promotes Cardiac Remodeling in Myocardial Infarction through the Activation of Endoplasmic Reticulum Stress |
title_sort | mitochondrial oxidative stress promotes cardiac remodeling in myocardial infarction through the activation of endoplasmic reticulum stress |
topic | cardiac fibrosis mitochondrial oxidative stress endoplasmic reticulum stress myocardial ischemia |
url | https://www.mdpi.com/2076-3921/11/7/1232 |
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