MicroRNA-Related Strategies to Improve Cardiac Function in Heart Failure

Heart failure (HF) describes a group of manifestations caused by the failure of heart function as a pump that supports blood flow through the body. MicroRNAs (miRNAs), as one type of non-coding RNA molecule, have crucial roles in the etiology of HF. Accordingly, miRNAs related to HF may represent potential novel therapeutic targets. In this review, we first discuss the different roles of miRNAs in the development and diseases of the heart. We then outline commonly used miRNA chemical modifications and delivery systems. Further, we summarize the opportunities and challenges for HF-related miRNA therapeutics targets, and discuss the first clinical trial of an antisense drug (CDR132L) in patients with HF. Finally, we outline current and future challenges and potential new directions for miRNA-based therapeutics for HF.

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Abstract 178: Metabolomic Approach by 1 H NMR Spectroscopy of Plasma for the Assessment of heart-function in Patients with Chronic Heart Failure

Circulation Research ◽

10.1161/res.113.suppl_1.a178 ◽

2013 ◽

Vol 113 (suppl_1) ◽

Author(s):

Wang Juan ◽

Luo Liangtao ◽

Li Zhongfeng ◽

Chen Jianxin ◽

Chen Chan ◽

...

Keyword(s):

Heart Failure ◽

Nmr Spectroscopy ◽

Chronic Heart Failure ◽

Heart Function ◽

Clinical Syndrome ◽

The Body ◽

Heart Failure Patients ◽

Nyha Classification ◽

Therapeutic Decisions ◽

Function Impairment

Chronic heart failure (CHF) is a progressive clinical syndrome characterized by inability of the heart to adequately pump blood to meet metabolic demands of the body, and assessment of heart function in chronic heart failure patients is needed to make therapeutic decisions. New York Heart Association( NYHA) classification is usually performed to evaluate heart-function of CHF patients. Nevertheless, this does not take into account metabolic perturbations produced by heart-function impairment. In contrast, metabolomics can investigate many metabolic perturbations within biological systems.The purpose of this study was to assess whether metabolomic profiles of plasma, obtained by proton NMR spectroscopy from CHF patients, are affected by the severity of heart-function impairment. An orthogonal projection to latent-structure analysis was performed to compare NMR spectra of 49 chronic heart failure patients according to NYHA classification.The statistical model obtained showed a good explained variance (R 2 X = 0.13 and R 2 Y = 0.92) and a good predictability (Q 2 Y = 0.68). Metabolomic profiles showed significant differences regarding various metabolites depending of severity of heart-function impairment: levels of high-density lipoprotein, glycol-protein, glutamine, glutamate, were significantly higher in patients with mild CHF compared to severe CHF. Other metabolites such as lactate and amino acids were significantly higher in patients with severe CHF than mild CHF. Our conclusion is that metabolomic NMR analysis provides new insights into metabolic processes related to the severity of heart function impairment in chronic heart failure.

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Immunopharmacology of Post-Myocardial Infarction and Heart Failure Medications

Journal of Clinical Medicine ◽

10.3390/jcm7110403 ◽

2018 ◽

Vol 7 (11) ◽

pp. 403 ◽

Cited By ~ 5

Author(s):

Mona Panahi ◽

Nimai Vadgama ◽

Mathun Kuganesan ◽

Fu Ng ◽

Susanne Sattler

Keyword(s):

Myocardial Infarction ◽

Heart Failure ◽

Immune Response ◽

Immune System ◽

Tissue Damage ◽

Heart Function ◽

The Body ◽

Inflammatory Conditions ◽

Drug Classes ◽

Potential Benefits

The immune system responds to acute tissue damage after myocardial infarction (MI) and orchestrates healing and recovery of the heart. However, excessive inflammation may lead to additional tissue damage and fibrosis and exacerbate subsequent functional impairment, leading to heart failure. The appreciation of the immune system as a crucial factor after MI has led to a surge of clinical trials investigating the potential benefits of immunomodulatory agents previously used in hyper-inflammatory conditions, such as autoimmune disease. While the major goal of routine post-MI pharmacotherapy is to support heart function by ensuring appropriate blood pressure and cardiac output to meet the demands of the body, several drug classes also affect a range of immunological pathways and modulate the post-MI immune response, which is crucial to take into account when designing future immunomodulatory trials. This review outlines how routine post-MI pharmacotherapy affects the immune response and may thus influence post-MI outcomes and development towards heart failure. Current key drug classes are discussed, including platelet inhibitors, statins, β-blockers, and renin–angiotensin–aldosterone inhibitors.

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Abstract 57: First Induced Heart Failure Model in Adult Zebrafish by Chronic Isoproterenol Treatment

Circulation Research ◽

10.1161/res.117.suppl_1.57 ◽

2015 ◽

Vol 117 (suppl_1) ◽

Author(s):

Mandy Kossack ◽

Hugo A Katus ◽

Patrick Most ◽

David Hassel

Keyword(s):

Heart Failure ◽

Cardiac Function ◽

Heart Function ◽

Adult Zebrafish ◽

Molecular Alteration ◽

Cardiac Model ◽

Elevated Expression ◽

Novel Therapeutic Strategies ◽

Heart Failure Model ◽

Novel Therapeutic

Impaired β-adrenergic signal transduction is a common molecular alteration found in heart failure (HF). Chronic catecholamine release and overstimulation of β-adrenergic receptors (β-ARs) in the failing heart results in their desensitization, largely mediated through upregulation of the G-protein coupled receptor kinase 2 (GRK2), and consequently to the progression into HF. Chronic activation of β-ARs by isoproterenol (iso) infusion efficiently induces HF in mice, while therapeutic targeting of GRK2 in HF animal models preserves cardiac function, highlighting their significance in HF progression. Zebrafish represents an established model to evaluate genetic causes of HF and to screen for novel therapeutic targets. However, the contribution of the β-A system in zebrafish models of HF is not known. We here systematically analyzed the effect of iso on heart function in larval and adult zebrafish. Larvae first responded to iso with 3 days of age (d). Here, β-AR stimulation resulted in the activation of conserved signaling components and in the induction of common stress responsive genes. Chronic β-AR stimulation for 5 days induced signs of HF accompanied by similar expression changes seen in mammals. As heart phenotypes are usually not analyzed in larval zebrafish beyond 3d, our data implicates that previous studies neglected a possible impact of β-AR signaling, particularly important when screening for therapeutic components. Adult zebrafish recently emerged as an attractive cardiac model, especially for regenerative medicine. Echocardiography revealed that in adult zebrafish hearts, iso robustly enhanced cardiac function. Chronic β-AR stimulation for 14 days efficiently induced HF symptoms. Consistent with mammals, we found reduced expression of β-ARs and elevated expression of GRK2 and ANP. Additionally, these fish develop essential characteristics accompanied with HF, including increased cell death and elevated inflammation. In conclusion, we show that β-AR function in zebrafish is comparable to that in mammals. Further, we present the first iso-induced HF model in adult zebrafish, thereby introducing adult zebrafish as a particularly valuable model to study the pathogenesis of HF and to test for novel therapeutic strategies to treat HF.

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Effect of traditional Asian exercise on patients with chronic heart failure: a protocol for network meta-analysis of randomised controlled trials

BMJ Open ◽

10.1136/bmjopen-2021-048891 ◽

2021 ◽

Vol 11 (8) ◽

pp. e048891

Author(s):

Jianglin Xu ◽

Zhuo Zhang ◽

Jing Liu ◽

Yan Li ◽

Lintong Yu ◽

...

Keyword(s):

Heart Failure ◽

Blood Pressure ◽

Randomised Controlled Trials ◽

Heart Function ◽

Meta Analysis ◽

The Body ◽

Controlled Trials ◽

Different Types ◽

Randomised Controlled

IntroductionChronic heart failure (CHF) is a common disease worldwide, and imposes a substantial burden to the healthcare system. In CHF, limited exercise capacity and affected mental well-being leads to a reduced quality of life (QOL). How to improve the QOL and exercise endurance is critical for patients with CHF. Exercise therapy, such as some traditional Asian exercises (TAEs) including Taichi, Baduanjin and Yoga, plays an important role in the rehabilitation of patients with CHF. TAE is suitable for the rehabilitation of patients with CHF because of its soft movements and can relax the body and mind. Studies have shown that TAE can regulate the overall health status of the body and exercise tolerance, improve QOL and reduce rehospitalisation rate in patients with CHF. However, the difference in efficacy of TAE in patients with CHF is not yet clear. The main purpose of this study is to conduct a network meta-analysis (NMA) of randomised trials to determine the impact of TAE on patients with CHF of different types, different causes and different New York Heart Association (NYHA) heart function classifications and to provide references for different types of patients with CHF to choose appropriate exercise rehabilitation therapy.Methods and analysisThe literature search will be retrieved from PubMed, the Cochrane Library, Embase, Web of Science, Chinese National Knowledge Infrastructure, Wanfang database, Chinese biomedical literature service system (SinoMed) and Chinese Scientific Journals Database (VIP) from the date of their inception until 1 August 2021. All randomised controlled trials that evaluated the effects of three different TAE therapies (Taichi, Baduanjin and Yoga) on patients with CHF will be included. The primary outcomes are peak oxygen uptake (peak VO2), exercise capacity (6-min walking distance) and QOL tested with the Minnesota Living with Heart Failure Questionnaire. Secondary outcomes include the levels of N-terminal pro brain natriuretic peptide, left ventricular ejection fraction, systolic blood pressure and diastolic blood pressure. For included articles, two reviewers will independently extract the data, and Cochrane Collaboration’s tool will be used to assess risk of bias. We will perform the Bayesian NMA to pool all treatment effects. The ranking probabilities for the optimal intervention of various treatments (Taichi, Baduanjin or Yoga) will be estimated by the mean ranks and surface under the cumulative ranking curve. Subgroup analysis for different types, different causes and different NYHA heart function classifications of CHF will be performed. We will use the Grading of Recommendations Assessment, Development and Evaluation system to assess the quality of evidence contributing to each network estimate.Ethics and disseminationThe results will be disseminated through peer-reviewed publications. They will provide useful information to inform clinicians on the potential functions of TAE in CHF, and to provide consolidated evidence for clinical practice and further research of TAE.PROSPERO registration numberCRD42020179304.

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Sensorless measurement of biological information in a magnetically levitated artificial heart and its application to QOL improvement technology

Impact ◽

10.21820/23987073.2019.10.70 ◽

2019 ◽

Vol 2019 (10) ◽

pp. 70-72

Author(s):

Wataru Hijikata

Keyword(s):

Heart Failure ◽

Blood Flow ◽

Continuous Flow ◽

Mechanical Engineering ◽

Heart Function ◽

Magnetic Bearing ◽

The Body ◽

Ventricular Assist Devices ◽

Mechanical Structure ◽

Flow Type

Heart disease is the leading cause of death in men and women around the world and it is a significant problem that requires remedy. Heart failure is where the heart is not pumping blood around the body as effectively as it should. Importantly, heart failure does not mean that the heart has stopped working, but it does require support in order to get it working better. Over the past few decades, there have been many innovations to help address the problems with heart failure, including developing ventricular assist devices (VADs). A VAD is a mechanical pump that is placed inside the body to support heart function and blood flow in heart patients. It works by taking blood from a lower chamber in the heart and pumping it to the body and vital organs, in the same way that a healthy heart would. Dr Wataru Hijikata is an expert in mechanical engineering and technology with a focus on healthcare outcomes. He explains that the first generation of VADs was a pulsatile flow type, but because of the complicated mechanical structure, the size of them was large and they had low durability. He notes that the second generation VAD was a continuous flow type. Because the blood flow was generated by the rotation of an impeller, the mechanical structure was simple and the size was small. However, the bearings to support the rotating impeller led to low durability. 'Third generation VADs are continuous flow types with contactless support of the impeller by magnetic bearing or hydrodynamic bearings,' Hijikata outlines. Owing to the contactless support technology, the durability of VADs has been enhanced and the size of the device is small. 'However, while there has been significant progress over the years, VADs are still far from perfect and there is much room for improvement,' he concludes. With that in mind, a team of researchers based at the Department of Mechanical Engineering in the Tokyo Institute of Technology, Japan, is investigating a means of improving VADs.

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CONGESTIVE HEART FAILURE SELF‐MANAGEMENT EDUCATION AND READMISSION AFTER HOSPITALIZATION

Malahayati International Journal of Nursing and Health Science ◽

10.33024/minh.v1i2.1036 ◽

2019 ◽

Vol 1 (2) ◽

pp. 59-62

Author(s):

Nurul Hidayah ◽

Eka Sakti Wahyuningtyas ◽

Iwan Shalahuddin

Keyword(s):

Heart Failure ◽

Congestive Heart Failure ◽

Management Education ◽

Heart Function ◽

Sampling Technique ◽

Statistical Test ◽

Expected Value ◽

The Body ◽

Self Management ◽

Chi Square

Background: Congestive Heart Failure (CHF) is a condition where the heart can no longer pump blood to the body tissues either to the entire body (systemic circulation) or to the lungs (pulmonary circulation). CHF is a clinical syndrome in patients with structural abnormalities and heart function. Heart function impairment may be a systolic or diastolic function disorder, heart rhythm disturbance, or preload and after load mismatch. This condition can cause death to the patient. Deaths from CHF range from 20-50% per year, in addition CHF is a disease that requires readmission . Frequency of CHF patient readmission by 45% per year.Purpose: This study aims to analyze the relationship of congestive heart failure self‐management education and readmission after hospitalizationMethods: The study was conducted at ICCU Tidar Magelang hospital with 27 CHF patients who had readmission. The sampling technique was done by consecutive sampling technique. Data analysis in this study using Chi square. The result of statistical test (Chi Square) shows that 2 cells (50%) with expected value <5 means the cells (boxes) whose expected value is below 5 by 50%. The minimum expected value of 2.07 means no expected value <1. Continuity Correction with p = 0,000. Fisher's Exact Test p value = 0,000.Resuts: The results of Symmetric Measure table (correlation test) obtained by the value of Contingency Coefficient (r) = 0.674 with p = 0,000.Conclusion: The conclusion of this statistical test is that there is a correlation between Experience of Self-Management Education (SME) and readmission of CHF patients.

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Direct measurement of vagal tone in rats does not show correlation to HRV

Scientific Reports ◽

10.1038/s41598-020-79808-8 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Joseph T. Marmerstein ◽

Grant A. McCallum ◽

Dominique M. Durand

Keyword(s):

Heart Failure ◽

Heart Rate ◽

Heart Rate Variability ◽

Neural Activity ◽

Vagal Tone ◽

Neural Recording ◽

The Body ◽

Autonomic Nerve ◽

Vagal Activity ◽

Recording Technology

AbstractThe vagus nerve is the largest autonomic nerve, innervating nearly every organ in the body. “Vagal tone” is a clinical measure believed to indicate overall levels of vagal activity, but is measured indirectly through the heart rate variability (HRV). Abnormal HRV has been associated with many severe conditions such as diabetes, heart failure, and hypertension. However, vagal tone has never been directly measured, leading to disagreements in its interpretation and influencing the effectiveness of vagal therapies. Using custom carbon nanotube yarn electrodes, we were able to chronically record neural activity from the left cervical vagus in both anesthetized and non-anesthetized rats. Here we show that tonic vagal activity does not correlate with common HRV metrics with or without anesthesia. Although we found that average vagal activity is increased during inspiration compared to expiration, this respiratory-linked signal was not correlated with HRV either. These results represent a clear advance in neural recording technology but also point to the need for a re-interpretation of the link between HRV and “vagal tone”.

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Rap1a Overlaps the AGE/RAGE Signaling Cascade to Alter Expression of α-SMA, p-NF-κB, and p-PKC-ζ in Cardiac Fibroblasts Isolated from Type 2 Diabetic Mice

Cells ◽

10.3390/cells10030557 ◽

2021 ◽

Vol 10 (3) ◽

pp. 557

Author(s):

Stephanie D. Burr ◽

James A. Stewart

Keyword(s):

Oxidative Stress ◽

Heart Failure ◽

Hydrogen Peroxide ◽

Cardiac Fibroblasts ◽

The Body ◽

Signaling Cascade ◽

Diabetic Mice ◽

Pkc Ζ ◽

Type 2 Diabetic

Cardiovascular disease, specifically heart failure, is a common complication for individuals with type 2 diabetes mellitus. Heart failure can arise with stiffening of the left ventricle, which can be caused by “active” cardiac fibroblasts (i.e., myofibroblasts) remodeling the extracellular matrix (ECM). Differentiation of fibroblasts to myofibroblasts has been demonstrated to be an outcome of AGE/RAGE signaling. Hyperglycemia causes advanced glycated end products (AGEs) to accumulate within the body, and this process is greatly accelerated under chronic diabetic conditions. AGEs can bind and activate their receptor (RAGE) to trigger multiple downstream outcomes, such as altering ECM remodeling, inflammation, and oxidative stress. Previously, our lab has identified a small GTPase, Rap1a, that possibly overlaps the AGE/RAGE signaling cascade to affect the downstream outcomes. Rap1a acts as a molecular switch connecting extracellular signals to intracellular responses. Therefore, we hypothesized that Rap1a crosses the AGE/RAGE cascade to alter the expression of AGE/RAGE associated signaling proteins in cardiac fibroblasts in type 2 diabetic mice. To delineate this cascade, we used genetically different cardiac fibroblasts from non-diabetic, diabetic, non-diabetic RAGE knockout, diabetic RAGE knockout, and Rap1a knockout mice and treated them with pharmacological modifiers (exogenous AGEs, EPAC, Rap1a siRNA, and pseudosubstrate PKC-ζ). We examined changes in expression of proteins implicated as markers for myofibroblasts (α-SMA) and inflammation/oxidative stress (NF-κB and SOD-1). In addition, oxidative stress was also assessed by measuring hydrogen peroxide concentration. Our results indicated that Rap1a connects to the AGE/RAGE cascade to promote and maintain α-SMA expression in cardiac fibroblasts. Moreover, Rap1a, in conjunction with activation of the AGE/RAGE cascade, increased NF-κB expression as well as hydrogen peroxide concentration, indicating a possible oxidative stress response. Additionally, knocking down Rap1a expression resulted in an increase in SOD-1 expression suggesting that Rap1a can affect oxidative stress markers independently of the AGE/RAGE signaling cascade. These results demonstrated that Rap1a contributes to the myofibroblast population within the heart via AGE/RAGE signaling as well as promotes possible oxidative stress. This study offers a new potential therapeutic target that could possibly reduce the risk for developing diabetic cardiovascular complications attributed to AGE/RAGE signaling.

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Right ventricular function and its coupling with the pulmonary circulation in acute heart failure

European Heart Journal ◽

10.1093/ehjci/ehaa946.1218 ◽

2020 ◽

Vol 41 (Supplement_2) ◽

Author(s):

M Barki ◽

M Losito ◽

M.M Caracciolo ◽

F Bandera ◽

M Rovida ◽

...

Keyword(s):

Heart Failure ◽

Acute Heart Failure ◽

Acute Phase ◽

Pulmonary Circulation ◽

Heart Function ◽

Systolic Pressure ◽

Left Ventricular ◽

Response To Treatment ◽

The Right ◽

B Lines

Abstract Background The right ventricle (RV) is extremely sensitive to hemodynamic changes and increased impedance. In acute heart failure (AHF), the development of pulmonary venous congestion and the increase of left ventricular (LV) filling pressures favors pulmonary vascular adverse remodeling and ultimately RV dysfunction, leading to the onset of symptoms and to a further decay of cardiac dynamics. Purpose The aim of the study was to evaluate RV morphology and functional dynamics at admission and discharge in patients hospitalized for AHF, analyzing the role and the response to treatment of the RV and its coupling with pulmonary circulation (PC). Methods Eighty-one AHF patients (mean age 75.75±10.6 years, 59% males) were prospectively enrolled within 24–48 hours from admission to the emergency department (ED). In either the acute phase and at pre-discharge all patients underwent M-Mode, 2-Dimensional and Doppler transthoracic echocardiography (TTE), as well as lung ultrasonography (LUS), to detect an increase of extravascular lung water (EVLW) and development of pleural effusion. Laboratory tests were performed in the acute phase and at pre-discharge including the evaluation of NT-proBNP. Results At baseline we observed a high prevalence of RV dysfunction as documented by a reduced RV systolic longitudinal function [mean tricuspid annular plane systolic excursion (TAPSE) at admission of 16.47±3.86 mm with 50% of the patients exhibiting a TAPSE<16mm], a decreased DTI-derived tricuspid lateral annular systolic velocity (50% of the subjects showed a tricuspid s' wave<10 cm/s) and a reduced RV fractional area change (mean FAC at admission of 36.4±14.6%). Furthermore, an increased pulmonary arterial systolic pressure (PASP) and a severe impairment in terms of RV coupling to PC was detected at initial evaluation (mean PASP at admission: 38.8±10.8 mmHg; average TAPSE/PASP at admission: 0.45±0.17 mm/mmHg). At pre-discharge a significant increment of TAPSE (16.47±3.86 mm vs. 17.45±3.88; p=0.05) and a reduction of PASP (38.8±10.8 mmHg vs. 30.5±9.6mmHg, p<0.001) was observed. Furthermore, in the whole population we assisted to a significant improvement in terms of RV function and its coupling with PC as demonstrated by the significant increase of TAPSE/PASP ratio (TAPSE/PASP: 0.45±0.17 mm/mmHg vs 0.62±0.20 mm/mmHg; p<0.001). Patients significantly reduced from admission to discharge the number of B-lines and NT-proBNP (B-lines: 22.2±17.1 vs. 6.5±5 p<0.001; NT-proBNP: 8738±948 ng/l vs 4227±659 ng/l p<0.001) (Figure 1). Nonetheless, no significant changes of left atrial and left ventricular dimensions and function were noted. Conclusions In AHF, development of congestion and EVLW significantly impact on the right heart function. Decongestion therapy is effective for restoring acute reversal of RV dysfunction, but the question remains on how to impact on the biological properties of the RV. Funding Acknowledgement Type of funding source: None

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