Role of endothelial PDGFB in arterio-venous malformations pathogenesis
AbstractArterial-venous malformations (AVMs) are direct connections between arteries and veins without an intervening capillary bed. Either familial inherited or sporadically occurring, localized pericytes (PCs) drop is among the AVMs ’ hallmarks. Whether impaired PC coverage triggers AVMs or it is a secondary event is unclear. Here we evaluated the role of the master regulator of PC recruitment, Platelet derived growth factor B (PDGFB) in AVM pathogenesis. Using tamoxifen-inducible deletion ofPdgfb in endothelial cells (ECs), we show that disruption of ECPdgfb-mediated PC recruitment and maintenance leads to capillary e...
Source: Angiogenesis - December 9, 2023 Category: Molecular Biology Source Type: research

Circulating Von Willebrand factor: a consistent biomarker predicting in-hospital mortality across different waves of the COVID-19 pandemic
(Source: Angiogenesis)
Source: Angiogenesis - December 9, 2023 Category: Molecular Biology Source Type: research

Role of endothelial PDGFB in arterio-venous malformations pathogenesis
AbstractArterial-venous malformations (AVMs) are direct connections between arteries and veins without an intervening capillary bed. Either familial inherited or sporadically occurring, localized pericytes (PCs) drop is among the AVMs ’ hallmarks. Whether impaired PC coverage triggers AVMs or it is a secondary event is unclear. Here we evaluated the role of the master regulator of PC recruitment, Platelet derived growth factor B (PDGFB) in AVM pathogenesis. Using tamoxifen-inducible deletion ofPdgfb in endothelial cells (ECs), we show that disruption of ECPdgfb-mediated PC recruitment and maintenance leads to capillary e...
Source: Angiogenesis - December 9, 2023 Category: Molecular Biology Source Type: research

Circulating Von Willebrand factor: a consistent biomarker predicting in-hospital mortality across different waves of the COVID-19 pandemic
(Source: Angiogenesis)
Source: Angiogenesis - December 9, 2023 Category: Molecular Biology Source Type: research

Multimodality imaging reveals angiogenic evolution in vivo during calvarial bone defect healing
AbstractThe healing of calvarial bone defects is a pressing clinical problem that involves the dynamic interplay between angiogenesis and osteogenesis within the osteogenic niche. Although structural and functional vascular remodeling (i.e., angiogenic evolution) in the osteogenic niche is a crucial modulator of oxygenation, inflammatory and bone precursor cells, most clinical and pre-clinical investigations have been limited to characterizing structural changes in the vasculature and bone. Therefore, we developed a new multimodality imaging approach that for the first time enabled the longitudinal (i.e., over four weeks) ...
Source: Angiogenesis - November 30, 2023 Category: Molecular Biology Source Type: research

Correction: The angiogenesis suppressor gene AKAP12 is under the epigenetic control of HDAC7 in endothelial cells
(Source: Angiogenesis)
Source: Angiogenesis - November 7, 2023 Category: Molecular Biology Source Type: research

Notch ligands are biomarkers of anti-TNF response in RA patients
AbstractNotch and its ligands play a critical role in rheumatoid arthritis (RA) pathogenesis. Hence, studies were conducted to delineate the functional significance of the Notch pathway in RA synovial tissue (ST) cells and the influence of RA therapies on their expression. Morphological studies reveal that JAG1, DLL4, and Notch1 are highly enriched in RA ST lining and sublining CD68+CD14+ M Φs. JAG1 and DLL4 transcription is jointly upregulated in RA MΦs reprogrammed by TLR4/5 ligation and TNF, whereas Syntenin-1 exposure expands JAG1, DLL4, and Notch1 expression levels in these cells. Single-cell RNA-seq data exhibit th...
Source: Angiogenesis - October 5, 2023 Category: Molecular Biology Source Type: research

Targeting the microenvironment in the treatment of arteriovenous malformations
AbstractExtracranial arteriovenous malformations (AVMs) are regarded as rare diseases and are prone to complications such as pain, bleeding, relentless growth, and high volume of shunted blood. Due to the high vascular pressure endothelial cells of AVMs are exposed to mechanical stress. To control symptoms and lesion growth pharmacological treatment strategies are urgently needed in addition to surgery and interventional radiology. AVM cells were isolated from three patients and exposed to cyclic mechanical stretching for 24  h. Thalidomide and bevacizumab, both VEGF inhibitors, were tested for their ability to prevent th...
Source: Angiogenesis - September 21, 2023 Category: Molecular Biology Source Type: research

A defined clathrin-mediated trafficking pathway regulates sFLT1/VEGFR1 secretion from endothelial cells
AbstractFLT1/VEGFR1 negatively regulates VEGF-A signaling and is required for proper vessel morphogenesis during vascular development and vessel homeostasis. Although a soluble isoform, sFLT1, is often mis-regulated in disease and aging, how sFLT1 is trafficked and secreted from endothelial cells is not well understood. Here we define requirements for constitutive sFLT1 trafficking and secretion in endothelial cells from the Golgi to the plasma membrane, and we show that sFLT1 secretion requires clathrin at or near the Golgi. Perturbations that affect sFLT1 trafficking blunted endothelial cell secretion and promoted intrac...
Source: Angiogenesis - September 11, 2023 Category: Molecular Biology Source Type: research

Executive summary of the 14th HHT international scientific conference
AbstractHereditary Hemorrhagic Telangiectasia (HHT) is an autosomal dominant vascular disorder characterized by small, dilated clustered vessels (telangiectasias) and by larger visceral arteriovenous malformations (AVMs), which directly connect the feeding arteries with the draining veins. These lesions are fragile, prone to rupture, and lead to recurrent epistaxis and/or internal hemorrhage among other complications. Germline heterozygous loss-of-function (LOF) mutations in Bone Morphogenic Protein 9 (BMP9) and BMP10 signaling pathway genes (endoglin-ENG, activin like kinase 1ACVRL1 akaALK1, andSMAD4) cause different subt...
Source: Angiogenesis - September 11, 2023 Category: Molecular Biology Source Type: research

A defined clathrin-mediated trafficking pathway regulates sFLT1/VEGFR1 secretion from endothelial cells
AbstractFLT1/VEGFR1 negatively regulates VEGF-A signaling and is required for proper vessel morphogenesis during vascular development and vessel homeostasis. Although a soluble isoform, sFLT1, is often mis-regulated in disease and aging, how sFLT1 is trafficked and secreted from endothelial cells is not well understood. Here we define requirements for constitutive sFLT1 trafficking and secretion in endothelial cells from the Golgi to the plasma membrane, and we show that sFLT1 secretion requires clathrin at or near the Golgi. Perturbations that affect sFLT1 trafficking blunted endothelial cell secretion and promoted intrac...
Source: Angiogenesis - September 11, 2023 Category: Molecular Biology Source Type: research