Aging Impairs Reverse Remodeling and Recovery of Ventricular Function after Isoproterenol-Induced Cardiomyopathy

Yáñez-Bisbe, Laia; García-Elías, Anna; Tajes, Marta; Almendros, Isaac; Rodríguez‐Sinovas, Antonio; Inserte, Javier; Ruiz‐Meana, Marisol; Farré, Ramón; Farré, Núria; Benito, Begoña

doi:10.3390/ijms23010174

Cited by 9 publications

(9 citation statements)

References 40 publications

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“…The aged heart undergoes a series of changes at the molecular level that leave it vulnerable to myocardial injury in cardiovascular diseases such as myocardial infarction and cardiomyopathy ( 22 , 23 ). In our study, we found that the expression of SP1, which is a transcription factor that is upstream of Cirbp , was decreased in aged donor hearts, leading to the attenuation of hypothermic cardioprotection.…”

Section: Discussionmentioning

confidence: 99%

Cirbp suppression compromises DHODH-mediated ferroptosis defense and attenuates hypothermic cardioprotection in an aged donor transplantation model

Zhu,

Jiang,

et al. 2024

Journal of Clinical Investigation

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Hypothermia is commonly used to protect donor hearts during transplantation. However, patients transplanted with aged donor hearts still have severe myocardial injury and decreased survival rates, but the underlying mechanism remains unknown. Because aged hearts are not considered suitable for donation, the number of patients awaiting heart transplants is increasing. In this study, we examined whether hypothermic cardioprotection was attenuated in aged donor hearts during transplantation and evaluated potential therapeutic targets. Using a rat heart transplantation model, we found that hypothermic cardioprotection was impaired in aged donor hearts but preserved in young donor hearts. RNA-Seq showed that cold-inducible RNA-binding protein ( Cirbp ) expression was decreased in aged donor hearts, and these hearts showed severe ferroptosis after transplantation. The young donor hearts from Cirbp -KO rats exhibited attenuated hypothermic cardioprotection, but Cirbp overexpression in aged donor hearts ameliorated hypothermic cardioprotection. Cardiac proteomes revealed that dihydroorotate dehydrogenase (DHODH) expression was significantly decreased in Cirbp -KO donor hearts during transplantation. Consequently, DHODH-mediated ubiquinone reduction was compromised, thereby exacerbating cardiac lipid peroxidation and triggering ferroptosis after transplantation. A cardioplegic solution supplemented with CIRBP agonists improved hypothermic cardioprotection in aged donor hearts, indicating that this method has the potential to broaden the indications for using aged donor hearts in transplantation.

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Section: Discussionmentioning

confidence: 99%

Cirbp suppression compromises DHODH-mediated ferroptosis defense and attenuates hypothermic cardioprotection in an aged donor transplantation model

Zhu,

Jiang,

et al. 2024

Journal of Clinical Investigation

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“…Similarly, Park et al found that patients with HFiEF were younger than those without ( 18 ). Furthermore, animal experiments suggested that aging animals showed persistent tissue fibrosis and cardiac dysfunction with impaired reverse remodeling, unlike younger animals that experienced complete cardiac function recovery ( 19 ). Older HF patients carry a higher risk of comorbidities such as diabetes mellitus, hypertension, and anemia, and are prone to significant calcification and multiple and diffuse lesions ( 11 , 20 ).…”

Section: Discussionmentioning

confidence: 99%

Development and Validation of a Novel Nomogram to Predict Improved Left Ventricular Ejection Fraction in Patients With Heart Failure After Successful Percutaneous Coronary Intervention for Chronic Total Occlusion

Guo

et al. 2022

Front. Cardiovasc. Med.

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BackgroundHeart failure with improved left ventricular ejection fraction (HFiEF) is linked to a good clinical outcome. The purpose of this study was to create an easy-to-use model to predict the occurrence of HFiEF in patients with heart failure (HF), 1 year after successful percutaneous coronary intervention (PCI) for chronic total occlusion (CTO) (CTO PCI).MethodsPatients diagnosed with HF who successfully underwent CTO PCI between January 2016 and August 2019 were included. To mitigate the effect of residual stenosis on left ventricular (LV) function, we excluded patients with severe residual stenosis, as quantitatively measured by a residual synergy between PCI with Taxus and Cardiac Surgery score (rSS) of >8. We gathered demographic data, medical history, angiographic and procedural characteristics, echocardiographic parameters, laboratory results, and medication information. The least absolute shrinkage and selection operator (LASSO) and multivariate logistic regression models were used to identify predictors of HFiEF 1 year after CTO revascularization. A nomogram was established and validated according to the area under the receiver operating characteristic curve (AUC) and calibration curves. Internal validation was performed using bootstrap resampling.ResultsA total of 465 patients were finally included in this study, and 165 (35.5%) patients experienced HFiEF 1 year after successful CTO PCI. According to the LASSO regression and multivariate logistic regression analyses, four variables were selected for the final prediction model: age [odds ratio (OR): 0.969; 95% confidence interval (CI): 0.952–0.988; p = 0.001], previous myocardial infarction (OR: 0.533; 95% CI: 0.357–0.796; p = 0.002), left ventricular end-diastolic dimension (OR: 0.940; 95% CI: 0.910–0.972; p < 0.001), and sodium glucose cotransporter two inhibitors (OR: 5.634; 95% CI: 1.756–18.080; p = 0.004). A nomogram was constructed to present the results. The C-index of the model was 0.666 (95% CI, 0.613–0.719) and 0.656 after validation. The calibration curve demonstrated that the nomogram agreed with the actual observations.ConclusionsWe developed an simple and effective nomogram for predicting the occurrence of HFiEF in patients with HF, 1 year after successful CTO PCI without severe residual stenosis.

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“…Second, we explored whether β-ecdysterone treatment affects the sympathetic central nervous system. We applied resting-state functional magnetic resonance imaging (rs-fMRI) to achieve real-time and non-invasive detection of whole brain activity [62][63][64] . Animal studies using rs-fMRI are often applied to nervous system diseases.…”

Section: Interdisplinary Investigation Of Central-peripheral Cardiova...mentioning

confidence: 99%

A functional medicine and food homology composition discovery based on disease-related target and data mining against cardiac remodeling

Xiao,

Li,

Qin

et al. 2024

Preprint

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Background: Medicine and food homological (MFH) products exhibit enhanced safety and tolerability, minimizing notable side effects, making them pivotal for prolonged use in cardiovascular diseases. This study aims to identify functional compounds in MFH based on cardiac remodeling-related target, employing reliable, comprehensive, and high-throughput methods. Methods: By bioinformatics and in vivo verifications, we initially investigated the key target in the progression of cardiac remodeling. Subsequently, we performed molecular docking among medical homology compound database (MHCD), and then performed drug-likeness evaluations to recognize functional component based on disease-related target. Pharmacological verifications and data mining including cardiac and medullary transcriptomics, neurotransmitter metabolomics, resting-state functional magnetic resonance imaging (rs-fMRI), and correlationship analysis were utilized to define the benefical effects of MFH functional components, as well as its in-depth mechanims. Results: The critical roles of oxidative stress and the key target of NRF2 in cardiac remodeling were discovered, and β-ecdysterone was screened as the most promising NRF2 enhancer in MHCD. Dose-dependent efficacy of β-ecdysterone in countering oxidative stress and ameliorating cardiac remodeling were then verfied by in vivo and ex vivo experiments. By data mining, the crosstalk mechanism between cardiac remodeling and neuromodulation was identified, and further unveiled Slc41a3 as a potential key factor influenced by β-ecdysterone. Additionally, β-ecdysterone mitigated increases in norepinephrine (NE) and its metabolites DHPG in the sympathetic nerve center hypothalamic paraventricular (PVN), as indicated by rs-fMRI. Cardiac and medullary transcriptomes revealed central-peripheral regulation signaling pathways during cardiac remodeling with the involvement of core gene of Dhx37. Conclusions: Our study identified β-ecdysterone as a natural MFH functional compound countering cardiac remodeling by targeting NRF2 elevation. It elucidates crosstalk between cardiac remodeling and neuromodulation, facilitating precise drug screening and mechanistic insights, providing substantial evidence for β-ecdysterone application and molecular mechanisms in cardiovascular diseases.

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Aging Impairs Reverse Remodeling and Recovery of Ventricular Function after Isoproterenol-Induced Cardiomyopathy

Cited by 9 publications

References 40 publications

Cirbp suppression compromises DHODH-mediated ferroptosis defense and attenuates hypothermic cardioprotection in an aged donor transplantation model

Cirbp suppression compromises DHODH-mediated ferroptosis defense and attenuates hypothermic cardioprotection in an aged donor transplantation model

Development and Validation of a Novel Nomogram to Predict Improved Left Ventricular Ejection Fraction in Patients With Heart Failure After Successful Percutaneous Coronary Intervention for Chronic Total Occlusion

A functional medicine and food homology composition discovery based on disease-related target and data mining against cardiac remodeling

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