Unlocking cardiac motion: assessing software and machine learning for single-cell and cardioid kinematic insights.

The heart coordinates its functional parameters for optimal beat-to-beat mechanical activity. Reliable detection and quantification of these parameters still represent a hot topic in cardiovascular research. Nowadays, computer vision allows the development of open-source algorithms to measure cellular kinematics.

Single-Cell RNA Sequencing Reveals Metabolic Stress-Dependent Activation of Cardiac Macrophages in a Model of Dyslipidemia-Induced Diastolic Dysfunction.

Background: Metabolic distress is often associated with heart failure with preserved ejection fraction (HFpEF) and represents a therapeutic challenge. Metabolism-induced systemic inflammation links comorbidities with HFpEF. How metabolic changes affect myocardial inflammation in the context of HFpEF is not known.

Cardiac Aging Is Promoted by Pseudohypoxia Increasing p300-Induced Glycolysis.

Background: Heart failure is typical in the elderly. Metabolic remodeling of cardiomyocytes underlies inexorable deterioration of cardiac function with aging: glycolysis increases at the expense of oxidative phosphorylation, causing an energy deficit contributing to impaired contractility. Better understanding of the mechanisms of this metabolic switching could be critical for reversing the condition.

Functional Characterisation of the Rare p.E1225K Variant, Segregating in a Brugada Syndrome Familial Case, in Human Cardiomyocytes from Pluripotent Stem Cells.

Brugada syndrome (BrS) is an inherited autosomal dominant cardiac channelopathy. Pathogenic rare mutations in the gene, encoding the alpha-subunit of the voltage-dependent cardiac Na channel protein (Nav1.5), are identified in 20% of BrS patients, affecting the correct function of the channel.

Synthetic recovery of impulse propagation in myocardial infarction via silicon carbide semiconductive nanowires.

Myocardial infarction causes 7.3 million deaths worldwide, mostly for fibrillation that electrically originates from the damaged areas of the left ventricle. Conventional cardiac bypass graft and percutaneous coronary interventions allow reperfusion of the downstream tissue but do not counteract the bioelectrical alteration originated from the infarct area.

Peptide-Based Targeting of the L-Type Calcium Channel Corrects the Loss-of-Function Phenotype of Two Novel Mutations of the Gene Associated With Brugada Syndrome.

Brugada syndrome (BrS) is an inherited arrhythmogenic disease that may lead to sudden cardiac death in young adults with structurally normal hearts. No pharmacological therapy is available for BrS patients. This situation highlights the urgent need to overcome current difficulties by developing novel groundbreaking curative strategies.

miR-128-3p Is a Novel Regulator of Vascular Smooth Muscle Cell Phenotypic Switch and Vascular Diseases.

Rationale: MicroRNAs (miRNAs, miRs) are small noncoding RNAs that modulate gene expression by negatively regulating translation of target genes. Although the role of several miRNAs in vascular smooth muscle cells (VSMCs) has been extensively characterized, the function of miRNA-128-3p (miR-128) is still unknown.

Objective: To determine if miR-128 modulates VSMC phenotype and to define the underlying mechanisms.

The K219T-Lamin mutation induces conduction defects through epigenetic inhibition of SCN5A in human cardiac laminopathy.

Mutations in LMNA, which encodes the nuclear proteins Lamin A/C, can cause cardiomyopathy and conduction disorders. Here, we employ induced pluripotent stem cells (iPSCs) generated from human cells carrying heterozygous K219T mutation on LMNA to develop a disease model. Cardiomyocytes differentiated from these iPSCs, and which thus carry K219T-LMNA, have altered action potential, reduced peak sodium current and diminished conduction velocity.

Inhalation of peptide-loaded nanoparticles improves heart failure.

Peptides are highly selective and efficacious for the treatment of cardiovascular and other diseases. However, it is currently not possible to administer peptides for cardiac-targeting therapy via a noninvasive procedure, thus representing scientific and technological challenges. We demonstrate that inhalation of small (<50 nm in diameter) biocompatible and biodegradable calcium phosphate nanoparticles (CaPs) allows for rapid translocation of CaPs from the pulmonary tree to the bloodstream and to the myocardium, where their cargo is quickly released.

Histone Methyltransferase G9a Is Required for Cardiomyocyte Homeostasis and Hypertrophy.

Background: Correct gene expression programming of the cardiomyocyte underlies the normal functioning of the heart. Alterations to this can lead to the loss of cardiac homeostasis, triggering heart dysfunction. Although the role of some histone methyltransferases in establishing the transcriptional program of postnatal cardiomyocytes during heart development has been shown, the function of this class of epigenetic enzymes is largely unexplored in the adult heart.

TGF-β (Transforming Growth Factor-β) Plays a Pivotal Role in Cardiac Myofibroblast Arrhythmogenicity.

Background: TGF-β (transforming growth factor-β) importantly contributes to cardiac fibrosis by controlling differentiation, migration, and collagen secretion of cardiac myofibroblasts. It is still elusive, however, to which extent TGF-β alters the electrophysiological phenotype of myofibroblasts and cardiomyocytes and whether it affects proarrhythmic myofibroblast-cardiomyocyte crosstalk observed in vitro.

Methods And Results: Patch-clamp recordings of cultured neonatal rat ventricular myofibroblasts revealed that TGF-β, applied for 24 to 48 hours at clinically relevant concentrations (≤2.

Peptidomimetic Targeting of Cavβ2 Overcomes Dysregulation of the L-Type Calcium Channel Density and Recovers Cardiac Function.

Background: L-type calcium channels (LTCCs) play important roles in regulating cardiomyocyte physiology, which is governed by appropriate LTCC trafficking to and density at the cell surface. Factors influencing the expression, half-life, subcellular trafficking, and gating of LTCCs are therefore critically involved in conditions of cardiac physiology and disease.

Methods: Yeast 2-hybrid screenings, biochemical and molecular evaluations, protein interaction assays, fluorescence microscopy, structural molecular modeling, and functional studies were used to investigate the molecular mechanisms through which the LTCC Cavβ2 chaperone regulates channel density at the plasma membrane.

Bioinspired negatively charged calcium phosphate nanocarriers for cardiac delivery of MicroRNAs.

Aim: To develop biocompatible and bioresorbable negatively charged calcium phosphate nanoparticles (CaP-NPs) as an innovative therapeutic system for the delivery of bioactive molecules to the heart.

Materials & Methods: CaP-NPs were synthesized via a straightforward one-pot biomineralization-inspired protocol employing citrate as a stabilizing agent and regulator of crystal growth. CaP-NPs were administered to cardiac cells in vitro and effects of treatments were assessed.

Electroactive polyurethane/siloxane derived from castor oil as a versatile cardiac patch, part II: HL-1 cytocompatibility and electrical characterizations.

In first part of this experiment, biocompatibility of the newly developed electroactive polyurethane/siloxane films containing aniline tetramer moieties was demonstrated with proliferation and differentiation of C2C12 myoblasts. Here we further assessed the cytocompatibility of the prepared samples with HL1-cell line, the electrophysiological properties and the patch clamp recording of the seeded cells over the selected electroactive sample. Presence of electroactive aniline tetramer in the structure of polyurethane/siloxane led to the increased expression of cardiac-specific genes of HL-1 cells involved in muscle contraction and electrical coupling.

Electroactive polyurethane/siloxane derived from castor oil as a versatile cardiac patch, part I: Synthesis, characterization, and myoblast proliferation and differentiation.

Tissue-engineered cardiac patch aims at regenerating an infarcted heart by improving cardiac function and providing mechanical support to the diseased myocardium. In order to take advantages of electroactivity, a new synthetic method was developed for the introduction of an electroactive oligoaniline into the backbone of prepared patches. For this purpose, a series of electroactive polyurethane/siloxane films containing aniline tetramer (AT) was prepared through sol-gel reaction of trimethoxysilane functional intermediate polyurethane prepolymers made from castor oil and poly(ethylene glycol).

Aggravation of cardiac myofibroblast arrhythmogeneicity by mechanical stress.

Aims: Myofibroblasts (MFBs) as appearing in the myocardium during fibrotic remodelling induce slow conduction following heterocellular gap junctional coupling with cardiomyocytes (CMCs) in bioengineered tissue preparations kept under isometric conditions. In this study, we investigated the hypothesis that strain as developed during diastolic filling of the heart chambers may modulate MFB-dependent slow conduction.

Methods And Results: Effects of defined levels of strain on single-cell electrophysiology (patch clamp) and impulse conduction in patterned growth cell strands (optical mapping) were investigated in neonatal rat ventricular cell cultures (Wistar) grown on flexible substrates.

Abolishing myofibroblast arrhythmogeneicity by pharmacological ablation of α-smooth muscle actin containing stress fibers.

Rationale: Myofibroblasts typically appear in the myocardium after insults to the heart like mechanical overload and infarction. Apart from contributing to fibrotic remodeling, myofibroblasts induce arrhythmogenic slow conduction and ectopic activity in cardiomyocytes after establishment of heterocellular electrotonic coupling in vitro. So far, it is not known whether α-smooth muscle actin (α-SMA) containing stress fibers, the cytoskeletal components that set myofibroblasts apart from resident fibroblasts, are essential for myofibroblasts to develop arrhythmogenic interactions with cardiomyocytes.

A protective antiarrhythmic role of ursodeoxycholic acid in an in vitro rat model of the cholestatic fetal heart.

Unlabelled: Intrahepatic cholestasis of pregnancy may be complicated by fetal arrhythmia, fetal hypoxia, preterm labor, and, in severe cases, intrauterine death. The precise etiology of fetal death is not known. However, taurocholate has been demonstrated to cause arrhythmia and abnormal calcium dynamics in cardiomyocytes.

Myofibroblasts induce ectopic activity in cardiac tissue.

Focal ectopic activity in cardiac tissue is a key factor in the initiation and perpetuation of tachyarrhythmias. Because myofibroblasts as present in fibrotic remodeled myocardia and infarct scars depolarize cardiomyocytes by heterocellular electrotonic interactions via gap junctions in vitro, we investigated using strands of cultured ventricular cardiomyocytes coated with myofibroblasts, whether this interaction might give rise to depolarization-induced abnormal automaticity. Whereas uncoated cardiomyocyte strands were invariably quiescent, myofibroblasts induced synchronized spontaneous activity in a density dependent manner.

Temporal variability of repolarization in rat ventricular myocytes paced with time-varying frequencies.

Adaptation of action potential duration (APD) to pacing cycle length (CL) has been previously characterized in isolated cardiomyocytes for sudden changes in constant CL and for pre-/postmature stimuli following constant pacing trains. However, random fluctuations characterize both physiological sinus rhythm (up to 10% of mean CL) and intrinsic beat-to-beat APD at constant pacing rate. We analysed the beat-to-beat sensitivity of each APD to the preceding CL during constant-sudden, random or linearly changing pacing trains in single patch clamped rat left ventricular myocytes, in the absence of the autonomic and electrotonic effects that modulate rate dependency in the intact heart.