Plasma levels of angiopoietin-2, VEGF-A, and VCAM-1 as markers of bevacizumab-induced hypertension: CALGB 80303 and 90401 (Alliance)
This study aimed to identify plasma proteins related to the function of the vasculature to predict the risk of severe bevacizumab-induced hypertension. Using pretreated plasma samples from 398 bevacizumab-treated patients in two clinical trials (CALGB 80303 and 90401), the levels of 17 proteins were measured via ELISA. The association between proteins and grade 3 bevacizumab-induced hypertension was performed by calculating the odds ratio (OR) from logistic regression adjusting for age, sex, and clinical trial. Using the optimal cut-point of each protein, sensitivity, specificity, positive predictive value (PPV), and negat...
Source: Angiogenesis - May 24, 2021 Category: Molecular Biology Source Type: research
Characterization of the heterogeneity of endothelial cells in bleomycin-induced lung fibrosis using single-cell RNA sequencing
AbstractThe loss of normal alveolar capillary and deregulated angiogenesis occurs simultaneously in idiopathic pulmonary fibrosis (IPF); however the contributions of specific endothelial subpopulations in the development of pulmonary fibrosis are poorly understood. Herein, we perform single-cell RNA sequencing to characterize the heterogeneity of endothelial cells (ECs) in bleomycin (BLM)-induced lung fibrosis in rats. One subpopulation, characterized by the expression of Nos3 and Cav1, is mostly distributed in non-fibrotic lungs and also highly expresses genes related to the “response to mechanical stimulus” and “lu...
Source: Angiogenesis - May 24, 2021 Category: Molecular Biology Source Type: research
Endothelial heterogeneity and plasticity
AbstractVascular endothelial cells are highly plastic and show great phenotypic heterogeneity. In recent years, emerging technologies have identified a range of novel endothelial phenotypes and functions. In this Special Issue of Angiogenesis, we present a series of papers from leading experts in the field, highlighting the heterogeneity and plasticity of endothelial cells in health and disease. (Source: Angiogenesis)
Source: Angiogenesis - May 20, 2021 Category: Molecular Biology Source Type: research
The endosomal RIN2/Rab5C machinery prevents VEGFR2 degradation to control gene expression and tip cell identity during angiogenesis
AbstractSprouting angiogenesis is key to many pathophysiological conditions, and is strongly regulated by vascular endothelial growth factor (VEGF) signaling through VEGF receptor 2 (VEGFR2). Here we report that the early endosomal GTPase Rab5C and its activator RIN2 prevent lysosomal routing and degradation of VEGF-bound, internalized VEGFR2 in human endothelial cells. Stabilization of endosomal VEGFR2 levels by RIN2/Rab5C is crucial for VEGF signaling through the ERK and PI3-K pathways, the expression of immediate VEGF target genes, as well as specification of angiogenic ‘tip’ and ‘stalk’ cell phenotypes and cell...
Source: Angiogenesis - May 13, 2021 Category: Molecular Biology Source Type: research
Von Willebrand factor collagen-binding capacity predicts in-hospital mortality in COVID-19 patients: insight from VWF/ADAMTS13 ratio imbalance
ConclusionVWF:CB levels could summarize both VWF increased levels and hyper-reactivity subsequent to ADAMTS13 overflow and, therefore, be a valuable and easy to perform clinical biomarker of microthrombosis and COVID-19 severity. (Source: Angiogenesis)
Source: Angiogenesis - May 11, 2021 Category: Molecular Biology Source Type: research
TAK1 signaling is a potential therapeutic target for pathological angiogenesis
AbstractAngiogenesis plays a critical role in both physiological responses and disease pathogenesis. Excessive angiogenesis can promote neoplastic diseases and retinopathies, while inadequate angiogenesis can lead to aberrant perfusion and impaired wound healing. Transforming growth factor β activated kinase 1 (TAK1), a member of the mitogen-activated protein kinase kinase kinase family, is a key modulator involved in a range of cellular functions including the immune responses, cell survival and death. TAK1 is activated in response to various stimuli such as proinflammatory cytokine s, hypoxia, and oxidative stress. Emer...
Source: Angiogenesis - May 10, 2021 Category: Molecular Biology Source Type: research
Notch regulates vascular collagen IV basement membrane through modulation of lysyl hydroxylase 3 trafficking
AbstractCollagen type IV (Col IV) is a basement membrane protein associated with early blood vessel morphogenesis and is essential for blood vessel stability. Defects in vascular Col IV deposition are the basis of heritable disorders, such as small vessel disease, marked by cerebral hemorrhage and drastically shorten lifespan. To date, little is known about how endothelial cells regulate the intracellular transport and selective secretion of Col IV in response to angiogenic cues, leaving a void in our understanding of this critical process. Our aim was to identify trafficking pathways that regulate Col IV deposition during...
Source: Angiogenesis - May 6, 2021 Category: Molecular Biology Source Type: research
High endothelial venules (HEVs) in immunity, inflammation and cancer
AbstractHigh endothelial venules (HEVs) are specialized blood vessels mediating lymphocyte trafficking to lymph nodes (LNs) and other secondary lymphoid organs. By supporting high levels of lymphocyte extravasation from the blood, HEVs play an essential role in lymphocyte recirculation and immune surveillance for foreign invaders (bacterial and viral infections) and alterations in the body ’s own cells (neoantigens in cancer). The HEV network expands during inflammation in immune-stimulated LNs and is profoundly remodeled in metastatic and tumor-draining LNs. HEV-like blood vessels expressing high levels of the HEV-speci...
Source: Angiogenesis - May 6, 2021 Category: Molecular Biology Source Type: research
The role of redox system in metastasis formation
AbstractThe metastatic cancer disease represents the real and urgent clinical need in oncology. Therefore, an understanding of the complex molecular mechanisms sustaining the metastatic cascade is critical to advance cancer therapies. Recent studies highlight how redox signaling influences the behavior of metastatic cancer cells, contributes to their travel in bloodstream from the primary tumor to the distant organs and conditions the progression of the micrometastases or their dormant state. Radical oxygen species not only regulate intracellular processes but participate to paracrine circuits by diffusion to nearby cells,...
Source: Angiogenesis - April 28, 2021 Category: Molecular Biology Source Type: research
Vascular endothelial cell specification in health and disease
AbstractThere are two vascular networks in mammals that coordinately function as the main supply and drainage systems of the body. The blood vasculature carries oxygen, nutrients, circulating cells, and soluble factors to and from every tissue. The lymphatic vasculature maintains interstitial fluid homeostasis, transports hematopoietic cells for immune surveillance, and absorbs fat from the gastrointestinal tract. These vascular systems consist of highly organized networks of specialized vessels including arteries, veins, capillaries, and lymphatic vessels that exhibit different structures and cellular composition enabling...
Source: Angiogenesis - April 12, 2021 Category: Molecular Biology Source Type: research
Adieu to parting Editor in Chief and pioneering scientist Dr. Joyce Bischoff
(Source: Angiogenesis)
Source: Angiogenesis - April 11, 2021 Category: Molecular Biology Source Type: research
Mechanisms and cell lineages in lymphatic vascular development
AbstractLymphatic vessels have critical roles in both health and disease and their study is a rapidly evolving area of vascular biology. The consensus on how the first lymphatic vessels arise in the developing embryo has recently shifted. Originally, they were thought to solely derive by sprouting from veins. Since then, several studies have uncovered novel cellular mechanisms and a diversity of contributing cell lineages in the formation of organ lymphatic vasculature. Here, we review the key mechanisms and cell lineages contributing to lymphatic development, discuss the advantages and limitations of experimental techniqu...
Source: Angiogenesis - April 6, 2021 Category: Molecular Biology Source Type: research
First blood: the endothelial origins of hematopoietic progenitors
AbstractHematopoiesis in vertebrate embryos occurs in temporally and spatially overlapping waves in close proximity to blood vascular endothelial cells. Initially, yolk sac hematopoiesis produces primitive erythrocytes, megakaryocytes, and macrophages. Thereafter, sequential waves of definitive hematopoiesis arise from yolk sac and intraembryonic hemogenic endothelia through an endothelial-to-hematopoietic transition (EHT). During EHT, the endothelial and hematopoietic transcriptional programs are tightly co-regulated to orchestrate a shift in cell identity. In the yolk sac, EHT generates erythro-myeloid progenitors, which...
Source: Angiogenesis - March 30, 2021 Category: Molecular Biology Source Type: research
SMAD6 transduces endothelial cell flow responses required for blood vessel homeostasis
AbstractFluid shear stress provided by blood flow instigates a transition from active blood vessel network expansion during development, to vascular homeostasis and quiescence that is important for mature blood vessel function. Here we show that SMAD6 is required for endothelial cell flow-mediated responses leading to maintenance of vascular homeostasis. Concomitant manipulation of the mechanosensor Notch1 pathway and SMAD6 expression levels revealed that SMAD6 functions downstream of ligand-induced Notch signaling and transcription regulation. Mechanistically, full-length SMAD6 protein was needed to rescue Notch loss-indu...
Source: Angiogenesis - March 29, 2021 Category: Molecular Biology Source Type: research
Depletion of Arg/Abl2 improves endothelial cell adhesion and prevents vascular leak during inflammation
AbstractEndothelial barrier disruption and vascular leak importantly contribute to organ dysfunction and mortality during inflammatory conditions like sepsis and acute respiratory distress syndrome. We identified the kinase Arg/Abl2 as a mediator of endothelial barrier disruption, but the role of Arg in endothelial monolayer regulation and its relevance in vivo remain poorly understood. Here we show that depletion of Arg in endothelial cells results in the activation of both RhoA and Rac1, increased cell spreading and elongation, redistribution of integrin-dependent cell-matrix adhesions to the cell periphery, and improved...
Source: Angiogenesis - March 26, 2021 Category: Molecular Biology Source Type: research
