Chemical and mechanical activation of resident cardiac macrophages in the living myocardial slice ex vivo model.

Resident cardiac macrophages (rcMACs) are among the most abundant immune cells in the heart. Plasticity and activation are hallmarks of rcMACs in response to changes in the microenvironment, which is essential for in vitro experimentation. The in vivo investigation is confounded by the infiltration of other cells hindering direct studies of rcMACs.

Development and characterization of anti-fibrotic natural compound similars with improved effectivity.

Cardiac fibroblasts constitute the major cell type of the murine and human heart. Once activated, they contribute to an excessive deposition of extracellular matrix (ECM) leading to cardiac fibrosis and subsequently organ dysfunction. With the exception of the pulmonary drugs, nintedanib and pirfenidone, drugs specifically targeting anti-fibrotic pathways are scarce.

Remodelling of adult cardiac tissue subjected to physiological and pathological mechanical load in vitro.

Aims: Cardiac remodelling is the process by which the heart adapts to its environment. Mechanical load is a major driver of remodelling. Cardiac tissue culture has been frequently employed for in vitro studies of load-induced remodelling; however, current in vitro protocols (e.

Combined high-throughput library screening and next generation RNA sequencing uncover microRNAs controlling human cardiac fibroblast biology.

Background: Myocardial fibrosis is a hallmark of the failing heart, contributing to the most common causes of deaths worldwide. Several microRNAs (miRNAs, miRs) controlling cardiac fibrosis were identified in recent years; however, a more global approach to identify miRNAs involved in fibrosis is missing.

Methods And Results: Functional miRNA mimic library screens were applied in human cardiac fibroblasts (HCFs) to identify annotated miRNAs inducing proliferation.

Integrative Bioinformatic Analyses of Global Transcriptome Data Decipher Novel Molecular Insights into Cardiac Anti-Fibrotic Therapies.

Integrative bioinformatics is an emerging field in the big data era, offering a steadily increasing number of algorithms and analysis tools. However, for researchers in experimental life sciences it is often difficult to follow and properly apply the bioinformatical methods in order to unravel the complexity and systemic effects of omics data. Here, we present an integrative bioinformatics pipeline to decipher crucial biological insights from global transcriptome profiling data to validate innovative therapeutics.

Cardiac endurance training alters plasma profiles of circular RNA MBOAT2.

Marathon running is an extreme physical activity, which determines cardiopulmonary adaption of athletes. Circular RNAs (circRNAs) as potential biomarkers in the blood stream have so far not been tested after such strenuous activities. In silico approaches were performed to identify the potential candidate circRNA MBOAT2.

Therapeutic modulation of RNA-binding protein Rbm38 facilitates re-endothelialization after arterial injury.

Aims: Delayed re-endothelialization after balloon angioplasty in patients with coronary or peripheral artery disease impairs vascular healing and leads to neointimal proliferation. In the present study, we examined the effect of RNA-binding motif protein 38 (Rbm38) during re-endothelialization in a murine model of experimental vascular injury.

Methods And Results: Left common carotid arteries of C57BL/6 mice were electrically denudated and endothelial regeneration was evaluated.

Identification of miR-143 as a Major Contributor for Human Stenotic Aortic Valve Disease.

Calcification of aortic valves leads to aortic stenosis mainly in elderly individuals, but the underlying molecular mechanisms are still not understood. Here, we studied microRNA (miR, miRNA) expression and function in healthy and stenotic human aortic valves. We identified miR-21, miR-24, and miR-143 to be highly upregulated in stenotic aortic valves.

Modelling IRF8 Deficient Human Hematopoiesis and Dendritic Cell Development with Engineered iPS Cells.

Human induced pluripotent stem (iPS) cells can differentiate into cells of all three germ layers, including hematopoietic stem cells and their progeny. Interferon regulatory factor 8 (IRF8) is a transcription factor, which acts in hematopoiesis as lineage determining factor for myeloid cells, including dendritic cells (DC). Autosomal recessive or dominant IRF8 mutations occurring in patients cause severe monocytic and DC immunodeficiency.

Cell fusion enhances mesendodermal differentiation of human induced pluripotent stem cells.

Human induced pluripotent stem cells (iPS cells) resemble embryonic stem cells and can differentiate into cell derivatives of all three germ layers. However, frequently the differentiation efficiency of iPS cells into some lineages is rather poor. Here, we found that fusion of iPS cells with human hematopoietic stem cells (HSCs) enhances iPS cell differentiation.

Dendritic cell development requires histone deacetylase activity.

DCs develop from multipotent progenitors (MPPs), which commit into DC-restricted common dendritic cell progenitors (CDPs). CDPs further differentiate into classical DCs (cDCs) and plasmacytoid DCs (pDCs). Here, we studied the impact of histone acetylation on DC development in C57BL/6 mice by interfering with histone acetylation and deacetylation, employing histone deacetylase (HDAC) inhibitors.