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.

Circulating neuregulin1-β in heart failure with preserved and reduced left ventricular ejection fraction.

Aims: Neuregulin1-β (NRG1-β) is released from microvascular endothelial cells in response to inflammation with compensatory cardioprotective effects. Circulating NRG1-β is elevated in heart failure (HF) with reduced ejection fraction (HFrEF) but not studied in HF with preserved EF (HFpEF).

Methods And Results: Circulating NRG1-β was quantified in 86 stable patients with HFpEF (EF ≥45% and N-terminal pro-brain natriuretic peptide >300 ng/L), in 86 patients with HFrEF prior to and after left ventricular assist device (LVAD) and/or heart transplantation (HTx) and in 21 healthy controls.

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.

Do You PrEP? A Review of Primary Care Provider Knowledge of PrEP and Attitudes on Prescribing PrEP.

Oral preexposure prophylaxis (PrEP) has been proven to be a safe and effective means of preventing HIV. The purpose of our literature review was to examine primary care provider knowledge and attitudes about prescribing PrEP. PubMed, CINAHL, Web of Science, and Scopus were searched and additional articles were identified through other sources, yielding 11 articles that met inclusion criteria.

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.

Costimulation blockade induces foxp3(+) regulatory T cells to human embryonic stem cells.

Transplantation of human embryonic stem cells (hESCs), like other allogeneic cellular transplants, require immunomodulation or immunosuppression in order to be maintained in the recipient. Costimulation blockade applied at the time of transplantation inhibits costimulatory signals in the immunological synapse leading to a state of anergy in the donor reactive T-cell population and a state of immunological tolerance in the host. In models of solid organ transplantation, tolerance is maintained by the infiltration of Foxp3(+) regulatory T cells into the graft.

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.

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(+).

Modulation of ephrinB2 leads to increased angiogenesis in ischemic myocardium and endothelial cell proliferation.

Eph/ephrin signaling is pivotal in prenatal angiogenesis while its potential role in postnatal angiogenesis largely remains to be explored. Therefore its putative angiogenic and therapeutic effects were explored in endothelium and in myocardial ischemia. In culture of human aortic endothelial cells the fusion protein ephrinB2-Fc induced cell proliferation (p<0.

Erythropoietin has an antiapoptotic effect after myocardial infarction and stimulates in vitro aortic ring sprouting.

Aims were to explore if darbepoietin-alpha in mouse can induce angiogenesis and if moderate doses after myocardial infarction stimulates periinfarct capillary and arteriolar densities, cell proliferation, and apoptosis. Myocardial infarction was induced by ligation of LAD. Mouse aortic rings (0.

Angiogenic effects of sequential release of VEGF-A165 and PDGF-BB with alginate hydrogels after myocardial infarction.

Objective: This study investigates whether local sequential delivery of vascular endothelial growth factor-A(165) (VEGF-A(165)) followed by platelet-derived growth factor-BB (PDGF-BB) with alginate hydrogels could induce an angiogenic effect and functional improvement greater than single factors after myocardial infarction.

Methods: Alginate hydrogels were prepared by combining high and low molecular weight alginate. Growth factor release rates were monitored over time in vitro with 125I-labelled VEGF-A(165) and PDGF-BB included in the gels.

Human mesenchymal stem cells do not differentiate into cardiomyocytes in a cardiac ischemic xenomodel.

Aim: As the capability of human mesenchymal stem cells (hMSC) to engraft, differentiate and improve myocardial function cannot be studied in humans, exploration was performed in a xenomodel.

Methods: The rats were divided into three groups depending on the type of rats used (Rowett nude (RNU) or Fischer rats +/- immunosuppression). Different groups were treated with intramyocardial injection of hMSC (1-2 million) either directly or three days after ligation of the left anterior descending artery (LAD).

Angiogenic and cardiac functional effects of dual gene transfer of VEGF-A165 and PDGF-BB after myocardial infarction.

Therapeutic angiogenesis is a potential treatment modality for myocardial ischemia. phVEGF-A(165), phPDGF-BB, or a combination of the two were injected into the myocardial infarct border zone in rats 7 days after ligation of the coronary left anterior descending artery. Cardiac function was measured by echocardiography.

Xenoreactivity and engraftment of human mesenchymal stem cells transplanted into infarcted rat myocardium.

Objective: It is thought that adult human mesenchymal stem cells do not induce immunoreactivity even to xenografts. We wanted to study whether adult human mesenchymal stem cells survive and engraft in experimentally induced ischemic rat myocardium.

Methods: Bone marrow-derived adult human mesenchymal stem cells (2.

Angiogenic effects of dual gene transfer of bFGF and PDGF-BB after myocardial infarction.

Therapeutic effects of combination of angiogenic growth factors for the treatment of ischemia after myocardial infarction are largely unknown. Plasmids expressing basic fibroblast growth factor (bFGF), platelet-derived growth factor (PDGF-BB) or their combination with a 1:1 mass ratio were injected into hearts with 7-day-old myocardial infarction. Hearts were harvested after 1 and 4 weeks after gene transfer.

Combination of angiopoietin-1 and vascular endothelial growth factor gene therapy enhances arteriogenesis in the ischemic myocardium.

We hypothesised that angiopoietin-1 (Ang-1), in conjunction with vascular endothelial growth factor (VEGF) gene therapy, can enhance arteriogenesis and angiogenesis during myocardial ischemia. Mice were given a single intramyocardial injection of saline, phVEGF-A(165) and phAng-1 or a combination thereof into the non-ischemic normal heart or into the ischemic border zone of the infarcted heart. In the normal and the ischemic myocardium, gene transfer of phVEGF-A(165) alone increased the myocardial capillary density by 16% and 36%, respectively, and phAng-1 had a similar effect.

Nonsurgical direct delivery of plasmid DNA into rat heart: time course, dose response, and the influence of different promoters on gene expression.

Transfer of genes encoding therapeutic proteins into the myocardium shows great potential for treatment of coronary artery disease. To quantitatively elucidate the behavior of plasmid DNA following cardiac gene transfer, time kinetics, dose-response relationship, systemic spread to the liver, and the influence of different promoters on plasmid DNA gene expression in rat hearts were examined using a novel nonsurgical direct delivery method that enables testing of large numbers of animals. Plasmids encoding either vascular endothelial growth factor A 165 or a fusion protein between enhanced green fluorescent protein (EGFP) luciferase were injected directly in rat hearts under echocardiographic guidance.

Protein and angiogenic dose-response expression of phVEGF-A(165) gene in rat myocardium.

Therapeutic myocardial angiogenesis by means of transient overexpression of angiogenic growth factors is a potential treatment modality for severe ischemic heart disease. This study was undertaken in the rat to examine effects of phVEGF-A(165) myocardial transfection in terms of dose-response as regards the number of hVEGF-A expressing cells on one hand and on the other angiogenesis. Non-surgical echocardiography-guided intramyocardial injection of phVEGF-A(165) was done into normoxic or hypoxic (10% O(2)) rats.

Extended-X-ray-absorption-fine-structure investigations of zinc in 5-aminolaevulinate dehydratase.

The zinc co-ordination in 5-aminolaevulinate dehydratase (5-aminolaevulinate hydro-lyase, EC 4.2.1.