Meis transcription factors regulate cardiac conduction system development and adult function.

Aims: The Cardiac Conduction System (CCS) is progressively specified during development by interactions among a discrete number of Transcriptions Factors that ensure its proper patterning and the emergence of its functional properties. Meis genes encode homeodomain transcription factors (TFs) with multiple roles in mammalian development. In humans, Meis genes associate with congenital cardiac malformations and alterations of cardiac electrical activity, however the basis for these alterations has not been established.

Morphological, electrophysiological, and molecular alterations in foetal noncompacted cardiomyopathy induced by disruption of ROCK signalling.

Left ventricular noncompaction cardiomyopathy is associated with heart failure, arrhythmia, and sudden cardiac death. The developmental mechanism underpinning noncompaction in the adult heart is still not fully understood, with lack of trabeculae compaction, hypertrabeculation, and loss of proliferation cited as possible causes. To study this, we utilised a mouse model of aberrant Rho kinase (ROCK) signalling in cardiomyocytes, which led to a noncompaction phenotype during embryogenesis, and monitored how this progressed after birth and into adulthood.

Participation of ventricular trabeculae in neonatal cardiac regeneration leads to ectopic recruitment of Purkinje-like cells.

Unlike adult mammals, newborn mice can regenerate a functional heart after myocardial infarction; however, the precise origin of the newly formed cardiomyocytes and whether the distal part of the conduction system (the Purkinje fiber (PF) network) is properly formed in regenerated hearts remains unclear. PFs, as well as subendocardial contractile cardiomyocytes, are derived from trabeculae, transient myocardial ridges on the inner ventricular surface. Here, using connexin 40-driven genetic tracing, we uncover a substantial participation of the trabecular lineage in myocardial regeneration through dedifferentiation and proliferation.

Electrical remodeling of atrioventricular junction: a study on retrogradely perfused chick embryonic heart.

Atrioventricular (AV) accessory pathways (APs) provide additional electrical connections between the atria and ventricles, resulting in severe electrical disturbances. It is generally accepted that APs originate in the altered annulus fibrosus maturation in the late prenatal and perinatal period. However, current experimental methods cannot address their development in specific locations around the annulus fibrosus because of the inaccessibility of late fetal hearts for electrophysiological investigation under physiological conditions.

Hepatoprotective and cardioprotective effects of empagliflozin in spontaneously hypertensive rats fed a high-fat diet.

A combination of liver and heart dysfunction worsens the prognosis of human survival. The aim of this study was to investigate whether empagliflozin (a sodium-glucose transporter-2 inhibitor) has beneficial effects not only on cardiac and renal function but also on hepatic function. Adult (6-month-old) male spontaneously hypertensive rats (SHR) were fed a high-fat diet (60% fat) for four months to induce hepatic steatosis and mild heart failure.

Developmental Aspects of Cardiac Adaptation to Increased Workload.

The heart is capable of extensive adaptive growth in response to the demands of the body. When the heart is confronted with an increased workload over a prolonged period, it tends to cope with the situation by increasing its muscle mass. The adaptive growth response of the cardiac muscle changes significantly during phylogenetic and ontogenetic development.

Development of ventricular trabeculae affects electrical conduction in the early endothermic heart.

Background: The ventricular trabeculae play a role, among others, in the impulse spreading in ectothermic hearts. Despite the morphological similarity with the early developing hearts of endotherms, this trabecular function in mammalian and avian embryos was poorly addressed.

Results: We simulated impulse propagation inside the looping ventricle and revealed delayed apical activation in the heart with inhibited trabecular growth.

Myocardial development in crocodylians.

Background: Recent reports confirmed the notion that there exists a rudimentary cardiac conduction system (CCS) in the crocodylian heart, and development of its ventricular part is linked to septation. We thus analyzed myocardial development with the emphasis on the CCS components and vascularization in two different crocodylian species.

Results: Using optical mapping and HNK-1 immunostaining, pacemaker activity was localized to the right-sided sinus venosus.

Development and diseases of the coronary microvasculature and its communication with the myocardium.

We review the current understanding of formation and development of the coronary microvasculature which supplies oxygen and nutrients to the heart myocardium and removes waste. We emphasize the close relationship, mutual development, and communication between microvasculature endothelial cells and surrounding cardiomyocytes. The first part of the review is focused on formation of microvasculature during embryonic development.

Coating Ti6Al4V implants with nanocrystalline diamond functionalized with BMP-7 promotes extracellular matrix mineralization in vitro and faster osseointegration in vivo.

The present study investigates the effect of an oxidized nanocrystalline diamond (O-NCD) coating functionalized with bone morphogenetic protein 7 (BMP-7) on human osteoblast maturation and extracellular matrix mineralization in vitro and on new bone formation in vivo. The chemical structure and the morphology of the NCD coating and the adhesion, thickness and morphology of the superimposed BMP-7 layer have also been assessed. The material analysis proved synthesis of a conformal diamond coating with a fine nanostructured morphology on the Ti6Al4V samples.

Excess ischemic tachyarrhythmias trigger protection against myocardial infarction in hypertensive rats.

Increased level of C-reactive protein (CRP) is a risk factor for cardiovascular diseases, including myocardial infarction and hypertension. Here, we analyzed the effects of CRP overexpression on cardiac susceptibility to ischemia/reperfusion (I/R) injury in adult spontaneously hypertensive rats (SHR) expressing human CRP transgene (SHR-CRP). Using an in vivo model of coronary artery occlusion, we found that transgenic expression of CRP predisposed SHR-CRP to repeated and prolonged ventricular tachyarrhythmias.

The Tale-Tell Heart: Evolutionary tetrapod shift from aquatic to terrestrial life-style reflected in heart changes in axolotl (Ambystoma mexicanum).

Background: During amphibian metamorphosis, the crucial moment lies in the rearrangement of the heart, reflecting the changes in circulatory demands. However, little is known about the exact shifts linked with this rearrangement. Here, we demonstrate such myocardial changes in axolotl (Ambystoma mexicanum) from the morphological and physiological point of view.

Tissue clearing and imaging methods for cardiovascular development.

Tissue imaging in 3D using visible light is limited and various clearing techniques were developed to increase imaging depth, but none provides universal solution for all tissues at all developmental stages. In this review, we focus on different tissue clearing methods for 3D imaging of heart and vasculature, based on chemical composition (solvent-based, simple immersion, hyperhydration, and hydrogel embedding techniques). We discuss in detail compatibility of various tissue clearing techniques with visualization methods: fluorescence preservation, immunohistochemistry, nuclear staining, and fluorescent dyes vascular perfusion.

Gap Junctional Communication via Connexin43 between Purkinje Fibers and Working Myocytes Explains the Epicardial Activation Pattern in the Postnatal Mouse Left Ventricle.

The mammalian ventricular myocardium forms a functional syncytium due to flow of electrical current mediated in part by gap junctions localized within intercalated disks. The connexin (Cx) subunit of gap junctions have direct and indirect roles in conduction of electrical impulse from the cardiac pacemaker via the cardiac conduction system (CCS) to working myocytes. Cx43 is the dominant isoform in these channels.

The formation of the atrioventricular conduction axis is linked in development to ventricular septation.

During development, the ventricles of mammals and birds acquire a specialized pattern of electrical activation with the formation of the atrioventricular conduction system (AVCS), which coincides with the completion of ventricular septation. We investigated whether AVCS formation coincides with ventricular septation in developing Siamese crocodiles (). Comparisons were made with Amazon toadhead turtle () with a partial septum only and no AVCS (negative control) and with chicken () (septum and AVCS, positive control).

HIF-1α is required for development of the sympathetic nervous system.

The molecular mechanisms regulating sympathetic innervation of the heart during embryogenesis and its importance for cardiac development and function remain to be fully elucidated. We generated mice in which conditional knockout (CKO) of the gene encoding the transcription factor hypoxia-inducible factor 1α (HIF-1α) is mediated by an transgene expressed in the cardiac outflow tract, right ventricle and atrium, pharyngeal mesoderm, peripheral neurons, and hindlimbs. These mice demonstrate significantly decreased perinatal survival and impaired left ventricular function.

Epoxyeicosatrienoic acid analog EET-B attenuates post-myocardial infarction remodeling in spontaneously hypertensive rats.

Epoxyeicosatrienoic acids (EETs) and their synthetic analogs have cardiovascular protective effects. Here, we investigated the action of a novel EET analog EET-B on the progression of post-myocardial infarction (MI) heart failure in spontaneously hypertensive rats (SHR). Adult male SHR were divided into vehicle- and EET-B (10 mg/kg/day; p.

Trabecular Architecture Determines Impulse Propagation Through the Early Embryonic Mouse Heart.

Most embryonic ventricular cardiomyocytes are quite uniform, in contrast to the adult heart, where the specialized ventricular conduction system is molecularly and functionally distinct from the working myocardium. We thus hypothesized that the preferential conduction pathway within the embryonic ventricle could be dictated by trabecular geometry. Mouse embryonic hearts of the Nkx2.

Haloperidol affects coupling between QT and RR intervals in guinea pig isolated heart.

Prolonged QT interval is an independent risk factor for development of ventricular arrhythmias. Haloperidol is one of the drugs inducing QT prolongation. Previous studies showed that haloperidol affects not only QT duration but also heart rate (RR interval).

Novel approaches to study coronary vasculature development in mice.

Background: Coronary artery development is an intensely studied field. Mice are a popular genetic model for developmental studies, but there is no widely accepted protocol for high-throughput, high-resolution imaging of their developmental and adult coronary artery anatomy.

Results: Using tissue-clearing protocols and confocal microscopy, we have analyzed embryonic and juvenile mouse hearts in Cx40:GFP knock-in models with a special focus on septal artery development.

Effect of increased left ventricle mass on ischemia assessment in electrocardiographic signals: rabbit isolated heart study.

Background: Detailed quantitative analysis of the effect of left ventricle (LV) hypertrophy on myocardial ischemia manifestation in ECG is still missing. The associations between both phenomena can be studied in animal models. In this study, rabbit isolated hearts with spontaneously increased LV mass were used to evaluate the effect of such LV alteration on ischemia detection criteria and performance.

Mechanistic Role of MicroRNAs in Coupling Lipid Metabolism and Atherosclerosis.

MicroRNAs (miRNAs, miRs) represent a group of powerful and versatile posttranscriptional regulators of gene expression being involved in the fine control of a plethora of physiological and pathological processes. Besides their well-established crucial roles in the regulation of cell cycle, embryogenesis or tumorigenesis, these tiny molecules have also been shown to participate in the regulation of lipid metabolism. In particular, miRs orchestrate cholesterol and fatty acids synthesis, transport, and degradation and low-density and high-density lipoprotein (LDL and HDL) formation.

Calcium versus strontium handling by the heart muscle.

Calcium plays a crucial role in numerous processes in living systems, from both intracellular and intercellular signalling to blood clotting. Calcium can be replaced by strontium in various intracellular processes due to high level of their similarity and strontium thus may serve as a valuable tool for different experimental studies. On the other hand, strontium is also used in clinical medicine and is commonly taken to the human body with food and water.

Long-Term Haloperidol Treatment Prolongs QT Interval and Increases Expression of Sigma 1 and IP3 Receptors in Guinea Pig Hearts.

Haloperidol is a neuroleptic drug used for a medication of various psychoses and deliria. Its administration is frequently accompanied by cardiovascular side effects, expressed as QT interval prolongation and occurrence of even lethal arrhythmias. Despite these side effects, haloperidol is still prescribed in Europe in clinical practice.