Diagnostic value of circulating microRNAs compared to high-sensitivity troponin T for the detection of non-ST-segment elevation myocardial infarction.

Aims: To assess the diagnostic value of microRNAs (miRNAs) for the detection of non-ST-segment elevation myocardial infarction (NSTEMI).

Methods And Results: A total of 1042 patients presenting between August 2014 and April 2017 to the emergency department with the suspected acute coronary syndrome were included. Non-ST-segment elevation myocardial infarction was diagnosed per criteria of the fourth Universal definition of myocardial infarction (UDMI) using high-sensitivity troponin T (hs-cTnT).

Novel aspects of age-protection by spermidine supplementation are associated with preserved telomere length.

Ageing provokes a plethora of molecular, cellular and physiological deteriorations, including heart failure, neurodegeneration, metabolic maladaptation, telomere attrition and hair loss. Interestingly, on the molecular level, the capacity to induce autophagy, a cellular recycling and cleaning process, declines with age across a large spectrum of model organisms and is thought to be responsible for a subset of age-induced changes. Here, we show that a 6-month administration of the natural autophagy inducer spermidine in the drinking water to aged mice is sufficient to significantly attenuate distinct age-associated phenotypes.

Reciprocal organ interactions during heart failure: a position paper from the ESC Working Group on Myocardial Function.

Heart failure-either with reduced or preserved ejection fraction (HFrEF/HFpEF)-is a clinical syndrome of multifactorial and gender-dependent aetiology, indicating the insufficiency of the heart to pump blood adequately to maintain blood flow to meet the body's needs. Typical symptoms commonly include shortness of breath, excessive fatigue with impaired exercise capacity, and peripheral oedema, thereby alluding to the fact that heart failure is a syndrome that affects multiple organ systems. Patients suffering from progressed heart failure have a very limited life expectancy, lower than that of numerous cancer types.

Renal AAV2-Mediated Overexpression of Long Non-Coding RNA Attenuates Ischemic Acute Kidney Injury Through Sponging of microRNA-30a-5p.

Background: Renal ischemia-reperfusion (I/R) injury is a major cause of AKI. Noncoding RNAs are intricately involved in the pathophysiology of this form of AKI. Transcription of hypoxia-induced, long noncoding RNA , which shows high embryonic expression and is silenced in adults, is upregulated in renal I/R injury.

Blood-based protein profiling identifies serum protein c-KIT as a novel biomarker for hypertrophic cardiomyopathy.

Hypertrophic cardiomyopathy (HCM) is one of the most common hereditary heart diseases and can be classified into an obstructive (HOCM) and non-obstructive (HNCM) form. Major characteristics for HCM are the hypertrophy of cardiomyocytes and development of cardiac fibrosis. Patients with HCM have a higher risk for sudden cardiac death compared to a healthy population.

DGK and DZHK position paper on genome editing: basic science applications and future perspective.

For a long time, gene editing had been a scientific concept, which was limited to a few applications. With recent developments, following the discovery of TALEN zinc-finger endonucleases and in particular the CRISPR/Cas system, gene editing has become a technique applicable in most laboratories. The current gain- and loss-of function models in basic science are revolutionary as they allow unbiased screens of unprecedented depth and complexity and rapid development of transgenic animals.

Circulating cardiovascular microRNAs in critically ill COVID-19 patients.

Aims: Coronavirus disease 2019 (COVID-19) is a still growing pandemic, causing many deaths and socio-economic damage. Elevated expression of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) entry receptor angiotensin-converting enzyme 2 on cardiac cells of patients with heart diseases may be related to cardiovascular burden. We have thus analysed cardiovascular and inflammatory microRNAs (miRs), sensitive markers of cardiovascular damage, in critically ill, ventilated patients with COVID-19 or influenza-associated acute respiratory distress syndrome (Influenza-ARDS) admitted to the intensive care unit and healthy controls.

Telomerase therapy attenuates cardiotoxic effects of doxorubicin.

Doxorubicin is one of the most potent chemotherapeutic agents. However, its clinical use is restricted due to the severe risk of cardiotoxicity, partially attributed to elevated production of reactive oxygen species (ROS). Telomerase canonically maintains telomeres during cell division but is silenced in adult hearts.

Resident cardiac macrophages: crucial modulators of cardiac (patho)physiology.

Resident cardiac macrophages (rcMacs) are integral components of the myocardium where they have key roles for tissue homeostasis and in response to inflammation, tissue injury and remodelling. In this review, we summarize the current knowledge and limitations associated with the rcMacs studies. We describe their specific role and contribution in various processes such as electrical conduction, efferocytosis, inflammation, tissue development, remodelling and regeneration in both the healthy and the disease state.

Novel antisense therapy targeting microRNA-132 in patients with heart failure: results of a first-in-human Phase 1b randomized, double-blind, placebo-controlled study.

Aims: Cardiac microRNA-132-3p (miR-132) levels are increased in patients with heart failure (HF) and mechanistically drive cardiac remodelling processes. CDR132L, a specific antisense oligonucleotide, is a first-in-class miR-132 inhibitor that attenuates and even reverses HF in preclinical models. The aim of the current clinical Phase 1b study was to assess safety, pharmacokinetics, target engagement, and exploratory pharmacodynamic effects of CDR132L in patients on standard-of-care therapy for chronic ischaemic HF in a randomized, placebo-controlled, double-blind, dose-escalation study (NCT04045405).

Pharmacokinetics and Proceedings in Clinical Application of Nucleic Acid Therapeutics.

Oligonucleotide therapeutics are a novel promising class of drugs designed to specifically target either coding or non-coding RNA molecules to revolutionize treatment of various diseases. During preclinical development, investigations of the pharmacokinetic characteristics of these oligonucleotide-based drug candidates are essential. Oligonucleotides possess a long history of chemical modifications to enhance their stability and binding affinity, as well as reducing toxicity.

Combined high-throughput library screening and next generation RNA sequencing uncover microRNAs controlling human cardiac fibroblast biology.

Background: Myocardial fibrosis is a hallmark of the failing heart, contributing to the most common causes of deaths worldwide. Several microRNAs (miRNAs, miRs) controlling cardiac fibrosis were identified in recent years; however, a more global approach to identify miRNAs involved in fibrosis is missing.

Methods And Results: Functional miRNA mimic library screens were applied in human cardiac fibroblasts (HCFs) to identify annotated miRNAs inducing proliferation.

Common mechanistic pathways in cancer and heart failure. A scientific roadmap on behalf of the Translational Research Committee of the Heart Failure Association (HFA) of the European Society of Cardiology (ESC).

The co-occurrence of cancer and heart failure (HF) represents a significant clinical drawback as each disease interferes with the treatment of the other. In addition to shared risk factors, a growing body of experimental and clinical evidence reveals numerous commonalities in the biology underlying both pathologies. Inflammation emerges as a common hallmark for both diseases as it contributes to the initiation and progression of both HF and cancer.

CDR132L improves systolic and diastolic function in a large animal model of chronic heart failure.

Aims: Cardiac miR-132 activation leads to adverse remodelling and pathological hypertrophy. CDR132L is a synthetic lead-optimized oligonucleotide inhibitor with proven preclinical efficacy and safety in heart failure (HF) early after myocardial infarction (MI), and recently completed clinical evaluation in a Phase 1b study (NCT04045405). The aim of the current study was to assess safety and efficacy of CDR132L in a clinically relevant large animal (pig) model of chronic heart failure following MI.

Heart Failure Association of the European Society of Cardiology update on sodium-glucose co-transporter 2 inhibitors in heart failure.

The Heart Failure Association (HFA) of the European Society of Cardiology (ESC) has recently issued a position paper on the role of sodium-glucose co-transporter 2 (SGLT2) inhibitors in heart failure (HF). The present document provides an update of the position paper, based of new clinical trial evidence. Accordingly, the following recommendations are given: • Canagliflozin, dapagliflozin empagliflozin, or ertugliflozin are recommended for the prevention of HF hospitalization in patients with type 2 diabetes mellitus and established cardiovascular disease or at high cardiovascular risk.

MicroRNAs as systemic biomarkers to assess distress in animal models for gastrointestinal diseases.

Severity assessment of animal experiments is mainly conducted by using subjective parameters. A widely applicable biomarker to assess animal distress could contribute to an objective severity assessment in different animal models. Here, the distress of three murine animal models for gastrointestinal diseases was assessed by multiple behavioral and physiological parameters.

A practical guide for investigating cardiac physiology using living myocardial slices.

Ex vivo multicellular preparations are essential tools to study tissue physiology. Among them, the recent methodological and technological developments in living myocardial slices (LMS) are attracting increasing interest by the cardiac research field. Despite this, this research model remains poorly perceived and utilized by most research laboratories.

Assessment of major mental disorders in a German peripartum cardiomyopathy cohort.

Aims: Peripartum cardiomyopathy (PPCM) is a heart disease affecting women during the last month of pregnancy or in the first months after delivery. The impact of the disease on mental health is largely unknown.

Methods And Results: Major mental disorders were assessed by a structured clinical interview in 40 patients with a confirmed PPCM diagnosis, and the data were compared with published prevalence in postpartum women.

MicroRNAs targeting the SARS-CoV-2 entry receptor ACE2 in cardiomyocytes.

The World Health Organization (WHO) declared coronavirus disease 2019 (COVID-19) as a public health emergency of international concern as more than 15 million cases were reported by 24th July 2020. Angiotensin-converting enzyme 2 (ACE2) is a COVID-19 entry receptor regulating host cell infection. A recent study reported that ACE2 is expressed in cardiomyocytes.

Aging impairs alveolar epithelial type II cell function in acute lung injury.

Morbidity and mortality rates in acute lung injury (ALI) increase with age. As alveolar epithelial type II cells (AE2) are crucial for lung function and repair, we hypothesized that aging promotes senescence in AE2 and contributes to the severity and impaired regeneration in ALI. ALI was induced with 2.

Association between Circular RNA CDR1as and Post-Infarction Cardiac Function in Pig Ischemic Heart Failure: Influence of the Anti-Fibrotic Natural Compounds Bufalin and Lycorine.

Anti-fibrotic therapies are of increasing interest to combat cardiac remodeling and heart failure progression. Recently, anti-fibrotic circular RNAs (circRNAs) have been identified in human and rodent cardiac tissue. In vivo (rodent) experiments proved cardiac anti-fibrotic effects of the natural compounds bufalin and lycorine by downregulating miRNA-671-5p, associated with a theoretic increase in the tissue level of circRNA CDR1as.

Improved cardiovascular risk prediction in patients with end-stage renal disease on hemodialysis using machine learning modeling and circulating microribonucleic acids.

To test whether novel biomarkers, such as microribonucleic acids (miRNAs), and nonstandard predictive models, such as decision tree learning, provide useful information for medical decision-making in patients on hemodialysis (HD). Samples from patients with end-stage renal disease receiving HD included in the AURORA trial were investigated (n=810). The study included two independent phases: phase I (matched cases and controls, n=410) and phase II (unmatched cases and controls, n=400).

Non-coding RNAs: emerging players in cardiomyocyte proliferation and cardiac regeneration.

Soon after birth, the regenerative capacity of the mammalian heart is lost, cardiomyocytes withdraw from the cell cycle and demonstrate a minimal proliferation rate. Despite improved treatment and reperfusion strategies, the uncompensated cardiomyocyte loss during injury and disease results in cardiac remodeling and subsequent heart failure. The promising field of regenerative medicine aims to restore both the structure and function of damaged tissue through modulation of cellular processes and regulatory mechanisms involved in cardiac cell cycle arrest to boost cardiomyocyte proliferation.