Spatially resolved multiomics on the neuronal effects induced by spaceflight in mice.

Impairment of the central nervous system (CNS) poses a significant health risk for astronauts during long-duration space missions. In this study, we employed an innovative approach by integrating single-cell multiomics (transcriptomics and chromatin accessibility) with spatial transcriptomics to elucidate the impact of spaceflight on the mouse brain in female mice. Our comparative analysis between ground control and spaceflight-exposed animals revealed significant alterations in essential brain processes including neurogenesis, synaptogenesis and synaptic transmission, particularly affecting the cortex, hippocampus, striatum and neuroendocrine structures.

High cardiomyocyte diversity in human early prenatal heart development.

Cardiomyocytes play key roles during cardiogenesis, but have poorly understood features, especially in prenatal stages. Here, we characterized human prenatal cardiomyocytes, 6.5-7 weeks post-conception, by integrating single-cell RNA sequencing, spatial transcriptomics, and ligand-receptor interaction information.

De novo spatiotemporal modelling of cell-type signatures in the developmental human heart using graph convolutional neural networks.

With the emergence of high throughput single cell techniques, the understanding of the molecular and cellular diversity of mammalian organs have rapidly increased. In order to understand the spatial organization of this diversity, single cell data is often integrated with spatial data to create probabilistic cell maps. However, targeted cell typing approaches relying on existing single cell data achieve incomplete and biased maps that could mask the true diversity present in a tissue slide.

A Spatiotemporal Organ-Wide Gene Expression and Cell Atlas of the Developing Human Heart.

The process of cardiac morphogenesis in humans is incompletely understood. Its full characterization requires a deep exploration of the organ-wide orchestration of gene expression with a single-cell spatial resolution. Here, we present a molecular approach that reveals the comprehensive transcriptional landscape of cell types populating the embryonic heart at three developmental stages and that maps cell-type-specific gene expression to specific anatomical domains.

Wnt/β-Catenin Stimulation and Laminins Support Cardiovascular Cell Progenitor Expansion from Human Fetal Cardiac Mesenchymal Stromal Cells.

The intrinsic regenerative capacity of human fetal cardiac mesenchymal stromal cells (MSCs) has not been fully characterized. Here we demonstrate that we can expand cells with characteristics of cardiovascular progenitor cells from the MSC population of human fetal hearts. Cells cultured on cardiac muscle laminin (LN)-based substrata in combination with stimulation of the canonical Wnt/β-catenin pathway showed increased gene expression of ISL1, OCT4, KDR, and NKX2.

Human fetal cardiac progenitors: The role of stem cells and progenitors in the fetal and adult heart.

The human fetal heart is formed early during embryogenesis as a result of cell migrations, differentiation, and formative blood flow. It begins to beat around gestation day 22. Progenitor cells are derived from mesoderm (endocardium and myocardium), proepicardium (epicardium and coronary vessels), and neural crest (heart valves, outflow tract septation, and parasympathetic innervation).

Meta-Analysis of Cell-based CaRdiac stUdiEs (ACCRUE) in patients with acute myocardial infarction based on individual patient data.

Rationale: The meta-Analysis of Cell-based CaRdiac study is the first prospectively declared collaborative multinational database, including individual data of patients with ischemic heart disease treated with cell therapy.

Objective: We analyzed the safety and efficacy of intracoronary cell therapy after acute myocardial infarction (AMI), including individual patient data from 12 randomized trials (ASTAMI, Aalst, BOOST, BONAMI, CADUCEUS, FINCELL, REGENT, REPAIR-AMI, SCAMI, SWISS-AMI, TIME, LATE-TIME; n=1252).

Methods And Results: The primary end point was freedom from combined major adverse cardiac and cerebrovascular events (including all-cause death, AMI recurrance, stroke, and target vessel revascularization).

Rosuvastatin inhibits TIMP-2 and promotes myocardial angiogenesis.

Background: Angiogenesis is usually driven by inflammation. Matrix metalloproteinases MMP-3 and MMP-9 and tissue inhibitors of metalloproteinases TIMP-1 and TIMP-2 are implicated in vascular remodeling. TIMP-2 exhibits antiangiogenic properties.

Plasma levels of stromal cell-derived factor-1 (CXCL12) and circulating endothelial progenitor cells in women with idiopathic heavy menstrual bleeding.

Study Question: Do plasma levels of stromal cell-derived factor-1 (CXCL12, sometimes termed SDF-1) and the numbers of circulating endothelial progenitor cells (EPCs), EPC colony-forming units (EPC-CFU) and mature endothelial cells (ECs) differ between women with idiopathic heavy menstrual bleeding of endometrial origin (HMB-E) and controls and are they related to plasma levels of other angiogenic growth factors?

Summary Answer: Angiogenesis is altered in women with HMB-E, characterized by a reduction in mean plasma levels of CXCL12, a low number of EPCs-CFUs and a high level of circulating ECs.

What Is Known Already: Plasma levels of CXCL12 are significantly higher during the proliferative than the secretory phase of the menstrual cycle in healthy women and exhibit a negative correlation with blood EPC-CFUs.

Study Design, Size, Duration: A prospective cohort study in a university hospital setting.

Relation between N-terminal pro-brain natriuretic peptide levels and response to enhanced external counterpulsation in chronic angina pectoris.

Objective: Although enhanced external counterpulsation (EECP) provides symptom reduction in many patients with severe angina pectoris, one-quarter of patients fail to respond. Earlier reports have not clearly established whether and how EECP responders may be identified pre-hoc. We hypothesized that clinical and biochemical data may be used to predict EECP response.

Electrocardiographic artefacts mimicking atrial tachycardia resulted in unnecessary diagnostic and therapeutic measures.

Electrocardiographic (ECG) artefacts may closely simulate both supraventricular and ventricular tachycardias. We describe a case initially diagnosed as rapid atrial fibrillation, based on 12-lead surface ECG (especially the limb leads) and monitor tracing. The arrhythmia was resistant to beta blockers.

Exploration of human, rat, and rabbit embryonic cardiomyocytes suggests K-channel block as a common teratogenic mechanism.

Aims: Several drugs blocking the rapidly activating potassium (K(r)) channel cause malformations (including cardiac defects) and embryonic death in animal teratology studies. In humans, these drugs have an established risk for acquired long-QT syndrome and arrhythmia. Recently, associations between cardiac defects and spontaneous abortions have been reported for drugs widely used in pregnancy (e.

Ischemia-reperfusion injury and pregnancy initiate time-dependent and robust signs of up-regulation of cardiac progenitor cells.

To explore how cardiac regeneration and cell turnover adapts to disease, different forms of stress were studied for their effects on the cardiac progenitor cell markers c-Kit and Isl1, the early cardiomyocyte marker Nkx2.5, and mast cells. Adult female rats were examined during pregnancy, after myocardial infarction and ischemia-reperfusion injury with/out insulin like growth factor-1(IGF-1) and hepatocyte growth factor (HGF).

Coronary artery perforation and regrowth of a side branch occluded by a polytetrafluoroethylene-covered stent implantation.

Stenting of the right coronary artery stenosis caused coronary perforation and profound dye (blood) extravasation in a 69-year-old female patient. Instantaneous balloon inflation followed by implantation of a polytetrafluoroethylene- (PTFE-)covered stent sealed the coronary perforation, restored the blood flow, and perceivably caused acute occlusion of a large side branch (SB). The immediate in situ balloon inflation prevented the development of cardiac tamponade.

Estrogen receptors do not influence angiogenesis after myocardial infarction.

Background: There is controversy on whether estrogen receptors are present and functioning in the myocardium. Aims. To explore if after myocardial infarction (MI) estrogen receptors α (ERα) and β (ERβ) are upregulated in myocardial tissue and to explore if the presence/ absence of ERα or ERβ influences angiogenesis after MI.

A Novel Descriptive, Intelligible and Ordered (DINO) classification of coronary bifurcation lesions. Review of current classifications.

Background: Several classification systems for coronary artery bifurcation lesions (CABL) have been described in the literature, but despite the commendable effort to simplify a difficult subject in interventional cardiology, all of them have certain limitations and shortcomings.

Methods And Results: The proposed Descriptive, INtelligible and Ordered (DINO) is a new descriptive and clinically oriented system of classifying CABLs. This classification system takes into consideration more details of the side branch angulation relative to the main branch.

Cyclic variability of stromal cell-derived factor-1 and endothelial progenitor cells during the menstrual cycle.

The endometrium goes through a unique cycle of physiological angiogenesis during the normal menstrual cycle (MC). We studied whether there is a correlation between endothelial progenitor cells (EPCs) and plasma and endometrial levels of angiogenic growth factors during the MC. Ten healthy, regularly menstruating women provided blood samples and another 16 supplied endometrial biopsies.

Anti-endothelial cell antibodies are increased in patients with previous myocardial infarction.

Objectives: Atherosclerosis is an inflammatory disease of multifactorial origin, in which immune cells together with metabolic risk factors may initiate, propagate, and activate lesions in the arterial tree. We investigated the role of auto-antibodies against endothelial cells in patients with previous myocardial infarction.

Design: One hundred and four patients were studied four to five years after acute myocardial infarction (aged 36-84 years) and 83 sex-matched healthy controls (aged 32-70 years).

Islet-1 cells are cardiac progenitors present during the entire lifespan: from the embryonic stage to adulthood.

The aim of this study was to longitudinally characterize the distribution of cells actively expressing the progenitor transcription factor islet-1 (Isl1+) during the embryonic life, the postnatal period, and adulthood. In this study, we have used direct immunohistochemical staining toward the protein Isl1 in a longitudinal rat model. Cells actively expressing Isl1 were traced in embryos from gestational day (GD) 11 until adulthood.

Depressed expression of angiogenic growth factors in the subacute phase of myocardial ischemia: a mechanism behind the remodeling plateau?

Background And Aims: To investigate whether, in the subacute phase of acute myocardial infarction, in the peri-infarcted area the expressions of the vascular endothelial growth factor (VEGF-A) and angiopoietin (Ang) ligand receptors are depressed, and whether overexpression of these angiogens counteracts a downregulation of myocardial function.

Methods: Acute myocardial infarction was induced by left anterior descending artery ligation and overexpression through injection of human VEGF-A165 and Ang-1 plasmids. The capillary and arteriolar densities, Akt-1 phosphorylation and citrate synthase activity were measured concurrent with the expression of VEGF-A, VEGFR1 and R2, Ang-1, Ang-2 and Tie-2.

Early first trimester human embryonic cardiac Islet-1 progenitor cells and cardiomyocytes: Immunohistochemical and electrophysiological characterization.

The aims of this study were to systematically characterize the distribution, proliferation, and differentiation of Islet-1(+)(Isl1(+)) progenitor cells in the early first trimester human embryonic heart during which period most of the organogenesis takes place. In hearts of gestational week 5 to 10 Isl1(+)cells were identified and mainly clustered in the outflow tract and to a lesser extent in the atria and in the right ventricle. Some of the clusters were also troponin T(+).

The ischemic preconditioning effect of adenosine in patients with ischemic heart disease.

Introduction: In vivo and in vitro evidence suggests that adenosine and its agonists play key roles in the process of ischemic preconditioning. The effects of low-dose adenosine infusion on ischemic preconditioning have not been thoroughly studied in humans.

Aims: We hypothesised that a low-dose adenosine infusion could reduce the ischemic burden evoked by physical exercise and improve the regional left ventricular (LV) systolic function.

Preconditioning effects of adenosine in patients with severe coronary artery disease but preserved coronary flow reserve.

Background: Adenosine plays a key role in different protective and adaptive responses to ischemia and has been suggested to induce ischemic preconditioning.

Aim: To investigate whether a low-dose adenosine infusion reduces the ischemic burden induced by pharmacological stress without affecting the coronary flow reserve (CFR).

Materials And Methods: Myocardial ischemia was induced by dobutamine stress test and quantified by tissue Doppler echocardiography in 11 patients with advanced coronary artery disease.