ACVR1/ALK2-p21 signaling axis modulates proliferation of the venous endothelium in the retinal vasculature.

The proliferation of the endothelium is a highly coordinated process to ensure the emergence, expansion, and homeostasis of the vasculature. While Bone Morphogenetic Protein (BMP) signaling fine-tunes the behaviors of endothelium in health and disease, how BMP signaling influences the proliferation of endothelium and therefore, modulates angiogenesis remains largely unknown. Here, we evaluated the role of Activin A Type I Receptor (ACVR1/ALK2), a key BMP receptor in the endothelium, in modulating the proliferation of endothelial cells.

BMP2 restores erectile dysfunction through neurovascular regeneration and fibrosis reduction in diabetic mice.

Background: The odds of erectile dysfunction are three times more prevalent in diabetes. Severe peripheral vascular and neural damage in diabetic patients responds poorly to phosphodiesterase-5 (PDE5) inhibitors. However, bone morphogenetic protein 2 is known to be involved in angiogenesis.

BMPR1A promotes ID2-ZEB1 interaction to suppress excessive endothelial to mesenchymal transition.

Aims: Components of bone morphogenetic protein (BMP) signalling have been implicated in both pathogenesis of pulmonary arterial hypertension (PAH) and endothelial-mesenchymal transition (EndoMT). In particular, the importance of BMP type 2 receptor in these processes has been extensively analysed. However, the contribution of BMP type 1 receptors (BMPR1s) to the onset of PAH and EndoMT remains poorly understood.

Endothelium-derived lactate is required for pericyte function and blood-brain barrier maintenance.

Endothelial cells differ from other cell types responsible for the formation of the vascular wall in their unusual reliance on glycolysis for most energy needs, which results in extensive production of lactate. We find that endothelium-derived lactate is taken up by pericytes, and contributes substantially to pericyte metabolism including energy generation and amino acid biosynthesis. Endothelial-pericyte proximity is required to facilitate the transport of endothelium-derived lactate into pericytes.

Ubiquitin-conjugating enzyme V variant 1 enables cellular responses toward fibroblast growth factor signaling in endothelium.

Ubiquitination has been shown to provide an essential regulatory role in modulating the duration and amplitude of the signaling activity in angiogenesis. While successive enzymatic reactions mediated by three distinct types of enzymes commonly known as E1, E2, and E3 are required for ubiquitination, the role of E3s which govern the final step of ubiquitination has been extensively analyzed in angiogenesis. In contrast, the role of E2s, which determine the context and functional consequences of ubiquitination, remains largely unknown with respect to angiogenesis.

Role of Venous Endothelial Cells in Developmental and Pathologic Angiogenesis.

Background: Angiogenesis is a dynamic process that involves expansion of a preexisting vascular network that can occur in a number of physiological and pathological settings. Despite its importance, the origin of the new angiogenic vasculature is poorly defined. In particular, the primary subtype of endothelial cells (capillary, venous, arterial) driving this process remains undefined.

The Role of BMP Signaling in Endothelial Heterogeneity.

Bone morphogenetic proteins (BMPs), which compose the largest group of the transforming growth factor-β (TGF-ß) superfamily, have been implied to play a crucial role in diverse physiological processes. The most intriguing feature of BMP signaling is that it elicits heterogeneous responses from cells with equivalent identity, thus permitting highly context-dependent signaling outcomes. In endothelial cells (ECs), which are increasingly perceived as a highly heterogeneous population of cells with respect to their morphology, function, as well as molecular characteristics, BMP signaling has shown to elicit diverse and often opposite effects, illustrating the innate complexity of signaling responses.

Somatic uniparental disomy mitigates the most damaging EFL1 allele combination in Shwachman-Diamond syndrome.

Shwachman-Diamond syndrome (SDS; OMIM #260400) is caused by variants in SBDS (Shwachman-Bodian-Diamond syndrome gene), which encodes a protein that plays an important role in ribosome assembly. Recent reports suggest that recessive variants in EFL1 are also responsible for SDS. However, the precise genetic mechanism that leads to EFL1-induced SDS remains incompletely understood.

Transcriptomic analysis identifies novel targets for individual bone morphogenetic protein type 1 receptors in endothelial cells.

Bone Morphogenetic Protein (BMP) signaling regulates diverse biological processes. Upon ligand binding, BMP receptors (BMPRs) phosphorylate SMAD1/5 and other noncanonical downstream effectors to induce transcription of downstream targets. However, the precise role of individual BMP receptors in this process remains largely unknown due to the complexity of downstream signaling and the innate promiscuity of ligand-receptor interaction.

Zebrafish as an Emerging Model for Dyslipidemia and Associated Diseases.

Dyslipidemia related diseases such as hyperlipidemia and atherosclerosis are the leading cause of death in humans. While cellular and molecular basis on the pathophysiology of dyslipidemia has been extensively investigated over decades, we still lack comprehensive understanding on the etiology of dyslipidemia due to the complexity and the innate multimodality of the diseases. While mouse has been the model organism of choice to investigate the pathophysiology of human dyslipidemia, zebrafish, a small freshwater fish which has traditionally used to study vertebrate development, has recently emerged as an alternative model organism.

Bone Morphogenetic Protein Signaling Restricts Proximodistal Extension of the Ventral Fin Fold.

Unpaired fins, which are the most ancient form of locomotory appendages in chordates, had emerged at least 500 million years ago. While it has been suggested that unpaired fins and paired fins share structural similarities, cellular and molecular mechanisms that regulate the outgrowth of the former have not been fully elucidated yet. Using the ventral fin fold in zebrafish as a model, here, we investigate how the outgrowth of the unpaired fin is modulated.

Analyses of Avascular Mutants Reveal Unique Transcriptomic Signature of Non-conventional Endothelial Cells.

Endothelial cells appear to emerge from diverse progenitors. However, to which extent their developmental origin contributes to define their cellular and molecular characteristics remains largely unknown. Here, we report that a subset of endothelial cells that emerge from the tailbud possess unique molecular characteristics that set them apart from stereotypical lateral plate mesoderm (LPM)-derived endothelial cells.

Pax9 is essential for granulopoiesis but dispensable for erythropoiesis in zebrafish.

Paired Box (Pax) gene family, a group of transcription regulators have been implicated in diverse physiological processes. However, their role during hematopoiesis which generate a plethora of blood cells remains largely unknown. Using a previously reported single cell transcriptomics data, we analyzed the expression of individual Pax family members in hematopoietic cells in zebrafish.

Comparison of transcriptomic changes between zebrafish and mice upon high fat diet reveals evolutionary convergence in lipid metabolism.

Hyperlipidemia is an abnormal elevation of lipid level in blood, which affects more than 100 million people in US. Zebrafish has recently emerged as a model to study pathophysiology associated with hyperlipidemia. As a poikilotherm, the innate response toward a high fat diet regimen in zebrafish is likely to be distinct from humans, and therefore, additional caution is warranted to appropriately interpret results obtained from zebrafish model.

Screening ginseng saponins in progenitor cells identifies 20(R)-ginsenoside Rh as an enhancer of skeletal and cardiac muscle regeneration.

Aging is associated with increased prevalence of skeletal and cardiac muscle disorders, such as sarcopenia and cardiac infarction. In this study, we constructed a compendium of purified ginsenoside compounds from Panax ginseng C.A.

Publisher Correction: Synergistic interaction of sprouting and intussusceptive angiogenesis during zebrafish caudal vein plexus development.

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.

Synergistic interaction of sprouting and intussusceptive angiogenesis during zebrafish caudal vein plexus development.

Intussusceptive angiogenesis (IA) is a complementary method to sprouting angiogenesis (SA). The hallmark of IA is formation of trans-capillary tissue pillars, their fusion and remodeling of the vascular plexus. In this study, we investigate the formation of the zebrafish caudal vein plexus (CVP) in Tg(fli1a:eGFP) and the synergistic interaction of IA and SA in crafting the archetypical angio-architecture of the CVP.

Corrigendum: Cloche is a bHLH-PAS transcription factor that drives haemato-vascular specification.

This corrects the article DOI: 10.1038/nature18614.

FGF-dependent metabolic control of vascular development.

Blood and lymphatic vasculatures are intimately involved in tissue oxygenation and fluid homeostasis maintenance. Assembly of these vascular networks involves sprouting, migration and proliferation of endothelial cells. Recent studies have suggested that changes in cellular metabolism are important to these processes.

Modulation of Endothelial Bone Morphogenetic Protein Receptor Type 2 Activity by Vascular Endothelial Growth Factor Receptor 3 in Pulmonary Arterial Hypertension.

Background: Bone morphogenetic protein (BMP) signaling has multiple roles in the development and function of the blood vessels. In humans, mutations in BMP receptor type 2 (BMPR2), a key component of BMP signaling, have been identified in the majority of patients with familial pulmonary arterial hypertension (PAH). However, only a small subset of individuals with mutation develops PAH, suggesting that additional modifiers of BMPR2 function play an important role in the onset and progression of PAH.

Notch regulates BMP responsiveness and lateral branching in vessel networks via SMAD6.

Functional blood vessel growth depends on generation of distinct but coordinated responses from endothelial cells. Bone morphogenetic proteins (BMP), part of the TGFβ superfamily, bind receptors to induce phosphorylation and nuclear translocation of SMAD transcription factors (R-SMAD1/5/8) and regulate vessel growth. However, SMAD1/5/8 signalling results in both pro- and anti-angiogenic outputs, highlighting a poor understanding of the complexities of BMP signalling in the vasculature.

Cell Electrical Impedance as a Novel Approach for Studies on Senescence Not Based on Biomarkers.

Senescence of cardiac myocytes is frequently associated with heart diseases. To analyze senescence in cardiac myocytes, a number of biomarkers have been isolated. However, due to the complex nature of senescence, multiple markers are required for a single assay to accurately depict complex physiological changes associated with senescence.

Natural product derivative BIO promotes recovery after myocardial infarction via unique modulation of the cardiac microenvironment.

The cardiac microenvironment includes cardiomyocytes, fibroblasts and macrophages, which regulate remodeling after myocardial infarction (MI). Targeting this microenvironment is a novel therapeutic approach for MI. We found that the natural compound derivative, BIO ((2'Z,3'E)-6-Bromoindirubin-3'-oxime) modulated the cardiac microenvironment to exert a therapeutic effect on MI.