Ischemic dilated cardiomyopathy pathophysiology through microRNA-16-5p

Calderón‐Domínguez, María; Mangas, Alipio; Belmonte, Thalía; Quezada-Feijoó, Maribel; Ramos, Mónica; Toro, Rocío

doi:10.1016/j.rec.2020.08.012

Cited by 13 publications

(21 citation statements)

References 41 publications

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“…Both mitral and tricuspid insufficiency were only detected in ICM patients. Finally, confirming the results from our previous work [43], expression levels of miR-16-5p were increased in the plasma of ICM patients.…”

Section: Patients and Control Subjectssupporting

confidence: 91%

“…Additionally, miRNAs have been identified as potential biomarkers of DCM, cardiac remodeling, and HF [41,42]. In this context, we have previously demonstrated that miR-16-5p is upregulated in the plasma of ICM patients [43]. Our in vitro studies showed that miR-16-5p promotes ER stress-induced apoptosis, autophagy, and inflammation in human ventricular myocytes [43].…”

Section: Introductionmentioning

confidence: 71%

“…In this context, we have previously demonstrated that miR-16-5p is upregulated in the plasma of ICM patients [43]. Our in vitro studies showed that miR-16-5p promotes ER stress-induced apoptosis, autophagy, and inflammation in human ventricular myocytes [43]. In the present study, we hypothesize that miR-16-5p might contribute to oxidative stress through ER stress induction and that targeting miR-16-5p may exert a cardioprotective role in ER stress-mediated cardiac injury.…”

Section: Introductionmentioning

confidence: 95%

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miR-16-5p Suppression Protects Human Cardiomyocytes against Endoplasmic Reticulum and Oxidative Stress-Induced Injury

Toro

Pérez‐Serra

Mangas

et al. 2022

IJMS

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Oxidative stress, defined as the excess production of reactive oxygen species (ROS) relative to antioxidant defense, plays a significant role in the development of cardiovascular diseases. Endoplasmic reticulum (ER) stress has emerged as an important source of ROS and its modulation could be cardioprotective. Previously, we demonstrated that miR-16-5p is enriched in the plasma of ischemic dilated cardiomyopathy (ICM) patients and promotes ER stress-induced apoptosis in cardiomyocytes in vitro. Here, we hypothesize that miR-16-5p might contribute to oxidative stress through ER stress induction and that targeting miR-16-5p may exert a cardioprotective role in ER stress-mediated cardiac injury. Analysis of oxidative markers in the plasma of ICM patients demonstrates that oxidative stress is associated with ICM. Moreover, we confirm that miR-16-5p overexpression promotes oxidative stress in AC16 cardiomyoblasts. We also find that, in response to tunicamycin-induced ER stress, miR-16-5p suppression decreases apoptosis, inflammation and cardiac damage via activating the ATF6-mediated cytoprotective pathway. Finally, ATF6 is identified as a direct target gene of miR-16-5p by dual-luciferase reporter assays. Our results indicate that miR-16-5p promotes ER stress and oxidative stress in cardiac cells through regulating ATF6, suggesting that the inhibition of miR-16-5p has potential as a therapeutic approach to protect the heart against ER and oxidative stress-induced injury.

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Section: Patients and Control Subjectssupporting

confidence: 91%

Section: Introductionmentioning

confidence: 71%

Section: Introductionmentioning

confidence: 95%

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miR-16-5p Suppression Protects Human Cardiomyocytes against Endoplasmic Reticulum and Oxidative Stress-Induced Injury

Toro

Pérez‐Serra

Mangas

et al. 2022

IJMS

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“…The significantly lower miRNA-16 expression levels in the maternal peripheral blood of women with PE compared to those without PE led epigenetic analysis in another direction. It is proposed, but not proven, that miRNA-16 plays a significant role in the progression of human cardiac cell injury in ischemic dilated cardiomyopathy through endoplasmic reticulum stress, inflammation, autophagy, and apoptosis (Calderon-Dominguez et al, 2021). Down regulation of this miRNA, known as an antiapoptotic factor, also was registered in ischemic myocardial cells, as a reaction to hypoxia in order to protect the tissue (Zhang H. J. et al, 2019).…”

Section: Discussionmentioning

confidence: 99%

Preeclamptic Women Have Disrupted Placental microRNA Expression at the Time of Preeclampsia Diagnosis: Meta-Analysis

Ćirković

Stanisavljević

Milin-Lazović

et al. 2021

Front. Bioeng. Biotechnol.

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Introduction: Preeclampsia (PE) is a pregnancy-associated, multi-organ, life-threatening disease that appears after the 20th week of gestation. The aim of this study was to perform a systematic review and meta-analysis to determine whether women with PE have disrupted miRNA expression compared to women who do not have PE.Methods: We conducted a systematic review and meta-analysis of studies that reported miRNAs expression levels in placenta or peripheral blood of pregnant women with vs. without PE. Studies published before October 29, 2021 were identified through PubMed, EMBASE and Web of Science. Two reviewers used predefined forms and protocols to evaluate independently the eligibility of studies based on titles and abstracts and to perform full-text screening, data abstraction and quality assessment. Standardized mean difference (SMD) was used as a measure of effect size.Results: 229 publications were included in the systematic review and 53 in the meta-analysis. The expression levels in placenta were significantly higher in women with PE compared to women without PE for miRNA-16 (SMD = 1.51,95%CI = 0.55–2.46), miRNA-20b (SMD = 0.89, 95%CI = 0.33–1.45), miRNA-23a (SMD = 2.02, 95%CI = 1.25–2.78), miRNA-29b (SMD = 1.37, 95%CI = 0.36–2.37), miRNA-155 (SMD = 2.99, 95%CI = 0.83–5.14) and miRNA-210 (SMD = 1.63, 95%CI = 0.69–2.58), and significantly lower for miRNA-376c (SMD = –4.86, 95%CI = –9.51 to –0.20). An increased level of miRNK-155 expression was found in peripheral blood of women with PE (SMD = 2.06, 95%CI = 0.35–3.76), while the expression level of miRNA-16 was significantly lower in peripheral blood of PE women (SMD = –0.47, 95%CI = –0.91 to –0.03). The functional roles of the presented miRNAs include control of trophoblast proliferation, migration, invasion, apoptosis, differentiation, cellular metabolism and angiogenesis.Conclusion: miRNAs play an important role in the pathophysiology of PE. The identification of differentially expressed miRNAs in maternal blood creates an opportunity to define an easily accessible biomarker of PE.

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“…Their evaluation could help with the differentiation of the etiology behind heart failure (ischemic vs. nonischemic) and possibly with the prediction of the future course of the disease [ 87 , 88 ]. Although current evidence is lacking, there are some small studies that discovered high plasma levels of miRNA-16 in patients with ischemic and familial dilated cardiomyopathy, confirming its relationship with these etiologies [ 89 , 90 , 91 ].…”

Section: Other Biomarkersmentioning

confidence: 99%

Well-Known and Novel Serum Biomarkers for Risk Stratification of Patients with Non-ischemic Dilated Cardiomyopathy

Anghel

Sascău

Zota

et al. 2021

IJMS

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Non-ischemic dilated cardiomyopathy encompasses a wide spectrum of myocardial disorders, characterized by left ventricular dilatation with systolic impairment and increased risk of sudden cardiac death. In spite of all the therapeutic progress that has been made in recent years, dilated cardiomyopathy continues to be an important cause of cardiac transplant, being associated with an enormous cost burden for health care systems worldwide. Predicting the prognosis of patients with dilated cardiomyopathy is essential to individualize treatment. Late gadolinium enhancement-cardiac magnetic resonance imaging, microvolt T-wave alternans, and genetic testing have emerged as powerful tools in predicting sudden cardiac death occurrence and maximizing patient’s selection. Despite all these new diagnostic modalities, additional tests to complement or replace current tools are required for better risk stratification. Therefore, biomarkers are an easy and important tool that can help to detect patients at risk of adverse cardiovascular events. Additionally, identifying potential biomarkers involved in dilated cardiomyopathy can provide us important information regarding the diagnostic, prognostic, risk stratification, and response to treatment for these patients. Many potential biomarkers have been studied in patients with dilated cardiomyopathy, but only a few have been adopted in current practice. Therefore, the aim of our review is to provide the clinicians with an update on the well-known and novel biomarkers that can be useful for risk stratification of patients with non-ischemic dilated cardiomyopathy.

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Ischemic dilated cardiomyopathy pathophysiology through microRNA-16-5p

Cited by 13 publications

References 41 publications

miR-16-5p Suppression Protects Human Cardiomyocytes against Endoplasmic Reticulum and Oxidative Stress-Induced Injury

miR-16-5p Suppression Protects Human Cardiomyocytes against Endoplasmic Reticulum and Oxidative Stress-Induced Injury

Preeclamptic Women Have Disrupted Placental microRNA Expression at the Time of Preeclampsia Diagnosis: Meta-Analysis

Well-Known and Novel Serum Biomarkers for Risk Stratification of Patients with Non-ischemic Dilated Cardiomyopathy

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