Telomerase is essential for cardiac differentiation and sustained metabolism of human cardiomyocytes.

Telomeres as the protective ends of linear chromosomes, are synthesized by the enzyme telomerase (TERT). Critically short telomeres essentially contribute to aging-related diseases and are associated with a broad spectrum of disorders known as telomeropathies. In cardiomyocytes, telomere length is strongly correlated with cardiomyopathies but it remains ambiguous whether short telomeres are the cause or the result of the disease.

Encapsulating In Vitro Transcribed circRNA into Lipid Nanoparticles Via Microfluidic Mixing.

This chapter serves as a guide for researchers embarking on circular RNA-based translational studies. It provides a foundation for the successful encapsulation of circular RNA into lipid nanoparticles (LNPs) and facilitates progress in this emerging field. Crucial scientific methods and techniques involved in the formulation process, particle characterization, and downstream processing of circ-LNPs are covered.

MicroRNA-centered theranostics for pulmoprotection in critical COVID-19.

Elucidating the pathobiological mechanisms underlying post-acute pulmonary sequelae following SARS-CoV-2 infection is essential for early interventions and patient stratification. Here, we investigated the potential of microRNAs (miRNAs) as theranostic agents for pulmoprotection in critical illness survivors. Multicenter study including 172 ICU survivors.

Myosin expression and contractile function are altered by replating stem cell-derived cardiomyocytes.

Myosin heavy chain (MyHC) is the main determinant of contractile function. Human ventricular cardiomyocytes (CMs) predominantly express the β-isoform. We previously demonstrated that ∼80% of human embryonic stem cell-derived cardiomyocytes (hESC-CMs) express exclusively β-MyHC after long-term culture on laminin-coated glass coverslips.

Multiformin-Type Azaphilones Prevent SARS-CoV-2 Binding to ACE2 Receptor.

Protein microarray screenings identified fungal natural products from the azaphilone family as potent inhibitors of SARS-CoV-2 spike protein binding to host ACE2 receptors. Cohaerin F, as the most potent substance from the cohaerin group, led to more than 50% less binding of ACE2 and SARS-CoV-2 spike protein. A survey for structurally related azaphilones yielded the structure elucidation of six new multiformins E-J (-) and the revision of the stereochemistry of the multiformins.

A circular RNA derived from the insulin receptor locus protects against doxorubicin-induced cardiotoxicity.

Aims: Cardiotoxicity leading to heart failure (HF) is a growing problem in many cancer survivors. As specific treatment strategies are not available, RNA discovery pipelines were employed and a new and powerful circular RNA (circRNA)-based therapy was developed for the treatment of doxorubicin-induced HF.

Methods And Results: The circRNA sequencing was applied and the highly species-conserved circRNA insulin receptor (Circ-INSR) was identified, which participates in HF processes, including those provoked by cardiotoxic anti-cancer treatments.

miR-486 attenuates cardiac ischemia/reperfusion injury and mediates the beneficial effect of exercise for myocardial protection.

Exercise and its regulated molecules have myocardial protective effects against cardiac ischemia/reperfusion (I/R) injury. The muscle-enriched miR-486 was previously identified to be upregulated in the exercised heart, which prompted us to investigate the functional roles of miR-486 in cardiac I/R injury and to further explore its potential in contributing to exercise-induced protection against I/R injury. Our data showed that miR-486 was significantly downregulated in the heart upon cardiac I/R injury.

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.

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.

Targeting muscle-enriched long non-coding RNA H19 reverses pathological cardiac hypertrophy.

Aims: Pathological cardiac remodelling and subsequent heart failure represents an unmet clinical need. Long non-coding RNAs (lncRNAs) are emerging as crucial molecular orchestrators of disease processes, including that of heart diseases. Here, we report on the powerful therapeutic potential of the conserved lncRNA H19 in the treatment of pathological cardiac hypertrophy.

Non-coding RNAs: update on mechanisms and therapeutic targets from the ESC Working Groups of Myocardial Function and Cellular Biology of the Heart.

Vast parts of mammalian genomes are actively transcribed, predominantly giving rise to non-coding RNA (ncRNA) transcripts including microRNAs, long ncRNAs, and circular RNAs among others. Contrary to previous opinions that most of these RNAs are non-functional molecules, they are now recognized as critical regulators of many physiological and pathological processes including those of the cardiovascular system. The discovery of functional ncRNAs has opened up new research avenues aiming at understanding ncRNA-related disease mechanisms as well as exploiting them as novel therapeutics in cardiovascular therapy.

Cyclin E and Cdk1 regulate the termination of germline transit-amplification process in testis.

An extension of the G1 is correlated with stem cell differentiation. The role of cell cycle regulation during the subsequent transit amplification (TA) divisions is, however, unclear. Here, we report for the first time that in the male germline lineage, the transit amplification divisions accelerate after the second TA division.

The Long Non-coding RNA Cyrano Is Dispensable for Pluripotency of Murine and Human Pluripotent Stem Cells.

Pluripotency is tightly regulated and is crucial for stem cells and their implementation for regenerative medicine. Non-coding RNAs, especially long non-coding RNAs (lncRNAs) emerged as orchestrators of versatile (patho)-physiological processes on the transcriptional and post-transcriptional level. Cyrano, a well-conserved lncRNA, is highly expressed in stem cells suggesting an important role in pluripotency, which we aimed to investigate in loss-off-function (LOF) experiments.

miR-21 and NT-proBNP Correlate with Echocardiographic Parameters of Atrial Dysfunction and Predict Atrial Fibrillation.

This study aimed to investigate the association of circulating biomarkers with echocardiographic parameters of atrial remodelling and their potential for predicting atrial fibrillation (AF). In patients with and without AF ( = 21 and = 60) the following serum biomarkers were determined: soluble ST2 (sST2), Galectin-3 (Gal-3), N-terminal pro-brain natriuretic peptide (NT-proBNP), microRNA (miR)-21, -29a, -133a, -146b and -328. Comprehensive transthoracic echocardiography was performed in all participants.

Preclinical development of a miR-132 inhibitor for heart failure treatment.

Despite proven efficacy of pharmacotherapies targeting primarily global neurohormonal dysregulation, heart failure (HF) is a growing pandemic with increasing burden. Treatments mechanistically focusing at the cardiomyocyte level are lacking. MicroRNAs (miRNA) are transcriptional regulators and essential drivers of disease progression.

Circulating Long Noncoding RNA LIPCAR Predicts Heart Failure Outcomes in Patients Without Chronic Kidney Disease.

The plasma levels of long noncoding RNA LIPCAR are elevated in heart failure (HF) patients with reduced ejection fraction and associated with left ventricular remodeling and poor outcomes. We studied whether the presence of chronic kidney disease (CKD), as defined by an estimated glomerular filtration rate value <60mL/(min·1.73m2) modified the associations of plasma LIPCAR with left ventricular remodeling and outcomes in HF patients.

Noncoding RNAs: potential regulators in cardioncology.

Cancer is the leading cause of morbidity and mortality in the United States and globally. Owing to improved early diagnosis and advances in oncological therapeutic options, the number of cancer survivors has steadily increased. Such efficient cancer therapies have also lead to alarming increase in cardiovascular complications in a significant proportion of cancer survivors, due to adverse cardiovascular effects such as cardiotoxicity, cardiac atrophy, and myocarditis.

Leukocyte telomere length correlates with hypertrophic cardiomyopathy severity.

Telomere length is a marker of biological aging. Short leukocyte telomere length has been associated with various conditions including cardiovascular disorders. Here, we evaluated if patients with hypertrophic cardiomyopathy have altered leukocyte telomere length and whether this is associated with disease severity.

Somatic ERK activation during transit amplification is essential for maintaining the synchrony of germline divisions in testis.

Transit amplification (TA) of progenitor cells maintains tissue homeostasis by balancing proliferation and differentiation. In testis, the germline proliferation is tightly regulated by factors present in both the germline and the neighbouring somatic cyst cells (SCCs). Although the exact mechanism is unclear, the epidermal growth factor receptor (EGFR) activation in SCCs has been reported to control spermatogonial divisions within a cyst, through downstream activations of Rac1-dependent pathways.

Quaking Inhibits Doxorubicin-Mediated Cardiotoxicity Through Regulation of Cardiac Circular RNA Expression.

Rationale: RBPs (RNA-binding proteins) have been described to be expressed and regulated in various organs including the heart. Little is known about the role of RBPs in heart failure induced by the chemotherapy drug doxorubicin and their interaction with circular RNAs.

Objective: We aimed to identify key RBPs involved in doxorubicin-mediated heart failure and to elucidate their function.

Linc-ing the Noncoding Genome to Heart Function: Beating Hypertrophy.

The principal event of aberrant gene expression occurs in numerous disorders and syndromes, including heart failure. LncRNAs may constitute powerful treatment targets because they intensively interact with their genetic environment, as they are important regulators of genetic networks. Recent advances on the functional roles of lncRNAs in cardiac hypertrophy are expected to usher improved therapeutic strategies.

Long Noncoding RNAs in Cardiovascular Pathology, Diagnosis, and Therapy.

Vast parts of mammalian genomes encode for transcripts that are not further translated into proteins. The purpose of the majority of such noncoding ribonucleic acids (RNAs) remained paradoxical for a long time. However, a growing body of evidence demonstrates that long noncoding RNAs are dynamically expressed in different cell types, diseases, or developmental stages to execute a wide variety of regulatory roles at virtually every step of gene expression and translation.