Targeting mir128-3p alleviates myocardial insulin resistance and prevents ischemia-induced heart failure

Ruiz-Velasco, Andrea; Zi, Min; Hille, Susanne; Azam, Tayyiba; Kaur, Namrita; Jiang, Juwei; Nguyen, Binh; Sekeres, Karolina; Binder, Pablo; Collins, Lucy; Pu, Fay; Xiao, Han; Guan, Kaomei; Frey, Norbert; Cartwright, Elizabeth J.; Müller, Oliver; Wang, Xin; Liu, Wei

doi:10.7554/elife.54298

Cited by 18 publications

(21 citation statements)

References 64 publications

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“…Furthermore, it is known that ERK5 is involved in insulin sensitivity in adipocytes [ 106 ]. Very recently, it has been published the implication of ERK5 in the preservation of IRS1 through the repression of mir128-3p under hypoxic conditions [ 107 ]. However, more efforts are needed to understand more deeply the effects of ERK5 in insulin resistance in the different tissues.…”

Section: Insulin Resistancementioning

confidence: 99%

Insulin Resistance and Diabetes Mellitus in Alzheimer’s Disease

Burillo

Marqués

Jiménez

et al. 2021

Cells

115

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Type 2 diabetes mellitus is a progressive disease that is characterized by the appearance of insulin resistance. The term insulin resistance is very wide and could affect different proteins involved in insulin signaling, as well as other mechanisms. In this review, we have analyzed the main molecular mechanisms that could be involved in the connection between type 2 diabetes and neurodegeneration, in general, and more specifically with the appearance of Alzheimer’s disease. We have studied, in more detail, the different processes involved, such as inflammation, endoplasmic reticulum stress, autophagy, and mitochondrial dysfunction.

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Section: Insulin Resistancementioning

confidence: 99%

Insulin Resistance and Diabetes Mellitus in Alzheimer’s Disease

Burillo

Marqués

Jiménez

et al. 2021

Cells

115

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“… 23 Moreover, as a key apoptosis-related element, recent studies have addressed miR-128 inhibition attenuates cardiomyocytes apoptosis and alleviate loss of cardiomyocytes following myocardial ischemia and hypertrophy, by targeting a multitude of ligand-activated transcription factor cascades, including SOX7/IL-33/sST2, PPARG/Akt/Mcl-1, and IRS1/CEBPβ/MAPK7/ signaling. 38–40 These findings altogether affirm the cardioprotective effect of miR-128 inhibition in the development of heart failure.…”

Section: Discussionmentioning

confidence: 63%

Upregulation of miR-128 Mediates Heart Injury by Activating Wnt/β-catenin Signaling Pathway in Heart Failure Mice

Tang

2021

Organogenesis

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Cardiac hypertrophy contributes to heart failure and is pathogenically modulated by a network of signaling cascades including Wnt/β-catenin signaling pathway. miRNAs have been widely demonstrated to regulate gene expression in heart development. miR-128 was routinely found as a brain-enriched gene and has been functionally associated with regulation of cardiac function. However, its role and molecular mechanisms that regulate cardiac hypertrophy remain largely unclear. Adeno-associated virus serotype 9 (AAV9)-mediated constructs with miR-128 or anti-miR-128 were generated and delivered to overexpression or blockade of miR-128 in vivo followed by HF induction with isoproterenol (ISO) or transverse aortic constriction (TAC). Cardiac dysfunction and hypertrophy, coupled with involved gene and protein level, were then assessed. Our data found that miR-128, Wnt1, and β-catenin expressions were upregulated in both patients and mice model with HF. Interference with miR-128 reduces Wnt1/β-catenin expression in mouse failing hearts and ameliorates heart dysfunctional properties. We identified miR-128 directly targets to Axin1, an inhibitor of Wnt/β-catenin signaling, and suppresses its inhibition on Wnt1/β-catenin. Our study provides evidence indicating miR-128 as an inducer of HF and cardiac hypertrophy by enhancing Wnt1/β-catenin in an Axin1-dependent nature. We thus suggest miR-128 has potential value in the treatment of heart failure.

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“…Third, the ability of the myocardium to utilize free fatty acids and glucose is correspondingly weakened during IR, which easily causes a series of metabolic disorders in the body and reduces the tolerance of the myocardium to ischemia 27 . Last but not the least, IR activates the sympathetic nervous system, enhances cardiac oxygen consumption, and aggravates myocardial injury 28 …”

Section: Discussionmentioning

confidence: 99%

Correlation analysis of the triglyceride glucose index and heart failure with preserved ejection fraction in essential hypertensive patients

Liao

Yang

et al. 2022

Clinical Cardiology

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Background: Triglyceride glucose index (TyG index) is a novel marker of insulin resistance. Studies have shown that TyG index is closely associated with the occurrence of hypertension and cardiovascular disease. However, little is known about the correlation between TyG index and the occurrence of heart failure with preserved ejection fraction (HFpEF) in hypertensive patients. Hypothesis: Our study assumes that TyG index strongly correlates with occurence of HFpEF in hypertensive patients. Methods: This research enrolled 559 hypertensive patients (273 patients with HFpEF and 286 without HFpEF) admitted to the Department of Cardiology of Jiading Branch of Shanghai General Hospital from 2020 to 2021 as the study subjects. Gender, age, diastolic blood pressure, systolic blood pressure (SBP), and heart rate (HR) were recorded at admission. Medication history and fasting blood samples were harvested after admission to detect laboratory index. Cardiac function and ventricular structure index were measured by echocardiography. Pearson correlation analysis was conducted to identify the correlation of TyG index with cardiac function and ventricular structure. The receiver operating characteristic (ROC) curve was used to evaluate the diagnostic value of TyG index in HFpEF with hypertension.Results: HFpEF patients had higher diuretic use frequencies, fasting plasma glucose, NT-proBNP, triglycerides, TyG index, left atrial diameter (LAD), left ventricular mass index (LVMI), the ratio of peak E-velocity of mitral orifice to peak velocity of early diastolic mitral annulus (E/e′), and SBP but lower ratio of peak E of early diastolic maximum blood flow velocity to peak A of late diastolic maximum blood flow velocity of mitral orifice (E/A) and average e′ than non-HFpEF patients. Moreover, TyG index was correlated with LAD, left ventricular ejection fraction (LVEF), LVMI, average e′, E/e′, and NT-proBNP. The multivariate regression analysis suggested that TyG index, E/e′, and NT-proBNP were independent risk factors for HFpEF in

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Targeting mir128-3p alleviates myocardial insulin resistance and prevents ischemia-induced heart failure

Cited by 18 publications

References 64 publications

Insulin Resistance and Diabetes Mellitus in Alzheimer’s Disease

Insulin Resistance and Diabetes Mellitus in Alzheimer’s Disease

Upregulation of miR-128 Mediates Heart Injury by Activating Wnt/β-catenin Signaling Pathway in Heart Failure Mice

Correlation analysis of the triglyceride glucose index and heart failure with preserved ejection fraction in essential hypertensive patients

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