RSF1 requires CEBP/ β and hSNF2H to promote IL-1β-mediated angiogenesis: the clinical and therapeutic relevance of RSF1 overexpression and amplification in myxofibrosarcomas
In conclusion, RSF1 overexpression, partly attributable toRSF1 amplification, contributes a novel proangiogenic function by partnering with CEBP/ β to cotransactivateIL1B, highlighting its prognostic, pathogenetic, and therapeutic relevance in myxofibrosarcomas. (Source: Angiogenesis)
Source: Angiogenesis - January 26, 2021 Category: Molecular Biology Source Type: research

A novel lymphatic pattern promotes metastasis of cervical cancer in a hypoxic tumour-associated macrophage-dependent manner
We describe these aggregates as LVEM (LVs encapsulated by TAMs) considering their advantageous metastatic capacity and active involvement in early lymph node metastasis (LNM). Mechanistic investigations revealed that interleukin-10 (IL-10) derived from hypoxic TAMs adjacent to LVs was a prerequisite for lymphangiogenesis and LVEM formation through its induction of Sp1 upregulation in lymphatic endothelial cells (LECs). Interestingly, Sp1high LECs promoted the transactivation of C –C motif chemokine ligand 1 (CCL1) to facilitate TAM and tumour cell recruitment, thereby forming a positive feedback loop to strengthen th...
Source: Angiogenesis - January 23, 2021 Category: Molecular Biology Source Type: research

Human endothelial colony-forming cells provide trophic support for pluripotent stem cell-derived cardiomyocytes via distinctively high expression of neuregulin-1
AbstractThe search for a source of endothelial cells (ECs) with translational therapeutic potential remains crucial in regenerative medicine. Human blood-derived endothelial colony-forming cells (ECFCs) represent a promising source of autologous ECs due to their robust capacity to form vascular networks in vivo and their easy accessibility from peripheral blood. However, whether ECFCs have distinct characteristics with translational value compared to other ECs remains unclear. Here, we show that vascular networks generated with human ECFCs exhibited robust paracrine support for human pluripotent stem cell-derived cardiomyo...
Source: Angiogenesis - January 17, 2021 Category: Molecular Biology Source Type: research

Circulating Von Willebrand factor and high molecular weight multimers as markers of endothelial injury predict COVID-19 in-hospital mortality
AbstractBackgroundCoronavirus disease 2019 (COVID-19) is a respiratory disease associated with endotheliitis and microthrombosis.ObjectivesTo correlate endothelial dysfunction to in-hospital mortality in a bi-centric cohort of COVID-19 adult patients.MethodsConsecutive ambulatory and hospitalized patients with laboratory-confirmed COVID-19 were enrolled. A panel of endothelial biomarkers and von Willebrand factor (VWF) multimers were measured in each patient ≤ 48 h following admission.ResultsStudy enrolled 208 COVID-19 patients of whom 23 were mild outpatients and 189 patients hospitalized after admission. M...
Source: Angiogenesis - January 15, 2021 Category: Molecular Biology Source Type: research

To be or not to be: endothelial cell plasticity in development, repair, and disease
AbstractEndothelial cells display an extraordinary plasticity both during development and throughout adult life. During early development, endothelial cells assume arterial, venous, or lymphatic identity, while selected endothelial cells undergo additional fate changes to become hematopoietic progenitor, cardiac valve, and other cell types. Adult endothelial cells are some of the longest-lived cells in the body and their participation as stable components of the vascular wall is critical for the proper function of both the circulatory and lymphatic systems, yet these cells also display a remarkable capacity to undergo chan...
Source: Angiogenesis - January 15, 2021 Category: Molecular Biology Source Type: research

RIPK3 modulates growth factor receptor expression in endothelial cells to support angiogenesis
AbstractReceptor-interacting protein kinase 3 (RIPK3) is a multifunctional intracellular protein that was first recognized as an important component of the necroptosis programmed cell death pathway. RIPK3 is also highly expressed in non-necroptotic murine embryonic endothelial cells (ECs) during vascular development, indicating its potential contribution to angiogenesis. To test this hypothesis, we generated mice lacking endothelial RIPK3 and found non-lethal embryonic and perinatal angiogenesis defects in multiple vascular beds. Our in vitro data indicate that RIPK3 supports angiogenesis by regulating growth factor recept...
Source: Angiogenesis - January 15, 2021 Category: Molecular Biology Source Type: research

Protection of capillaries may be critical in delaying aging around the eyes and prevention of facial plastic surgery
(Source: Angiogenesis)
Source: Angiogenesis - January 15, 2021 Category: Molecular Biology Source Type: research

YAP promotes ocular neovascularization by modifying PFKFB3-driven endothelial glycolysis
AbstractOcular neovascularization is the leading cause of vision impairment in a variety of ocular diseases, such as age-related macular degeneration and retinopathy of prematurity. Emerging studies have suggested that the yes-associated protein (YAP), a downstream effector of the Hippo pathway, is involved in the pathological angiogenesis, but the mechanism are largely unknown. Here, we demonstrated that hypoxic treatment triggered YAP expression and nuclear translocation in human umbilical vein endothelial cells (HUVECs). YAP acted as a transcriptional co-activator working together with transcriptional enhancer activator...
Source: Angiogenesis - January 5, 2021 Category: Molecular Biology Source Type: research

Oral itraconazole for epistaxis in hereditary hemorrhagic telangiectasia: a proof of concept study
In conclusion, oral itraconazole significantly improved epistaxis in HHT patients. The potential benefit of itraconazole in HHT should be further investigated. (Source: Angiogenesis)
Source: Angiogenesis - November 19, 2020 Category: Molecular Biology Source Type: research

Endothelium-specific deletion of Nox4 delays retinal vascular development and mitigates pathological angiogenesis
AbstractNADPH oxidase 4 (Nox4) is a major isoform of NADPH oxidases playing an important role in many biological processes. Previously we have shown that Nox4 is highly expressed in retinal blood vessels and is upregulated in oxygen-induced retinopathy (OIR). However, the exact role of endothelial Nox4 in retinal angiogenesis remains elusive. Herein, using endothelial cell (EC)-specific Nox4 knockout (Nox4EC −KO) mice, we investigated the impact of endothelial Nox4 deletion on retinal vascular development and pathological angiogenesis during OIR. Our results show that deletion of Nox4 in ECs led to retarded retinal v...
Source: Angiogenesis - November 17, 2020 Category: Molecular Biology Source Type: research

Talin-dependent integrin activation is required for endothelial proliferation and postnatal angiogenesis
AbstractIntegrin activation contributes to key blood cell functions including adhesion, proliferation and migration. An essential step in the cell signaling pathway that activates integrin requires the binding of talin to the β-integrin cytoplasmic tail. Whereas this pathway is understood in platelets in detail, considerably less is known regarding how integrin-mediated adhesion in endothelium contributes to postnatal angiogenesis. We utilized an inducible EC-specific talin1 knock-out mouse (Tln1 EC-KO) and talin1 L325R knock-in mutant (Tln1 L325R) mouse, in which talin selectively lacks the capacity to activate integ...
Source: Angiogenesis - October 28, 2020 Category: Molecular Biology Source Type: research

Microvascular dysfunction in COVID-19: the MYSTIC study
ConclusionsOur data clearly show severe alterations of the microcirculation and the endothelial glycocalyx in patients with COVID-19. Future therapeutic approaches should consider the importance of systemic vascular involvement in COVID-19. (Source: Angiogenesis)
Source: Angiogenesis - October 14, 2020 Category: Molecular Biology Source Type: research

Tubulin carboxypeptidase activity of vasohibin-1 inhibits angiogenesis by interfering with endocytosis and trafficking of pro-angiogenic factor receptors
AbstractReceptor endocytosis is crucial for integrating extracellular stimuli of pro-angiogenic factors, including vascular endothelial growth factor (VEGF), into the cell via signal transduction. VEGF not only triggers various angiogenic events including endothelial cell (EC) migration, but also induces the expression of negative regulators of angiogenesis, including vasohibin-1 (VASH1). While we have previously reported that VASH1 inhibits angiogenesis in vitro and in vivo, its mode of action on EC behavior remains elusive. Recently VASH1 was shown to have tubulin carboxypeptidase (TCP) activity, mediating the post-trans...
Source: Angiogenesis - October 14, 2020 Category: Molecular Biology Source Type: research

Angiogenesis, hereditary hemorrhagic telangiectasia and COVID-19
AbstractHereditary hemorrhagic telangiectasia (HHT) is a rare autosomal-dominant disease characterized by pathologic angiogenesis that provokes vascular overgrowth. The evidence about the influence of Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) in patients with rare diseases is scarce. We aimed to know the prevalence of coronavirus disease 2019 (COVID-19) in HHT patients. The HHT pathogenic angiogenesis and endothelial injury in COVID-19 are discussed using data from RiHHTa (Computerized Registry of Hereditary Hemorrhagic Telangiectasia) registry. RiHHTa is an open, multicenter, prospective, observational registr...
Source: Angiogenesis - October 14, 2020 Category: Molecular Biology Source Type: research

3D analysis of microvasculature in murine liver fibrosis models using synchrotron radiation-based microtomography
AbstractCirrhosis describes the development of excess fibrous tissue around regenerative nodules in response to chronic liver injury and usually leads to irreversible organ damage and end-stage liver disease. During the development of cirrhosis, the formation of collagenous scar tissue is paralleled by a reorganization and remodeling of the hepatic vascular system. To date, macrovascular remodeling in various cirrhosis models has been examined using three-dimensional (3D) imaging modalities, while microvascular changes have been studied mainly by two-dimensional (2D) light microscopic and electron microscopic imaging. Here...
Source: Angiogenesis - October 10, 2020 Category: Molecular Biology Source Type: research

Vessel tech: a high-accuracy pipeline for comprehensive mouse retinal vasculature characterization
AbstractMouse retinal vasculature is a well-recognized and commonly used animal model for angiogenesis and microvascular remodeling. Morphological features of retinal vasculature reflect the vessel ’s biological functions, and are critical in understanding the physiological and pathological process of vascular development and disease. Here we developed a comprehensive software,Vessel Tech, using retinal vasculature images of postnatal mice. This pipeline can automatically process retinal vascular images, reconstruct vessel network with high accuracy and assess global and local vascular characteristics based on the re...
Source: Angiogenesis - October 9, 2020 Category: Molecular Biology Source Type: research

BMP6/TAZ-Hippo signaling modulates angiogenesis and endothelial cell response to VEGF
AbstractThe BMP/TGF β-Smad, Notch and VEGF signaling guides formation of endothelial tip and stalk cells. However, the crosstalk of bone morphogenetic proteins (BMPs) and vascular endothelial growth factor receptor 2 (VEGFR2) signaling has remained largely unknown. We demonstrate that BMP family members regulate VEGFR 2 and Notch signaling, and act via TAZ-Hippo signaling pathway. BMPs were found to be regulated after VEGF gene transfer in C57/Bl6 mice and in a porcine myocardial ischemia model. BMPs 2/4/6 were identified as endothelium-specific targets of VEGF. BMP2 modulated VEGF-mediated endothelial sprouting via D...
Source: Angiogenesis - October 5, 2020 Category: Molecular Biology Source Type: research

Piwi-interacting RNAs (piRNAs) as potential biomarkers and therapeutic targets for cardiovascular diseases
AbstractCardiovascular diseases (CVDs) are the leading causes of death worldwide. Increasing reports demonstrated that non-coding RNAs (ncRNAs) have been crucially involved  in the development of CVDs. Piwi-interacting RNAs (piRNAs) are a novel cluster of small non-coding RNAs with strong uracil bias at the 5′ end and 2′-O-methylation at the 3 ′ end that are mainly present in the mammalian reproductive system and stem cells and serve as potential modulators of developmental and pathophysiological processes. Recently, piRNAs have been reported to be widely expressed in human tissues and can potentiall...
Source: Angiogenesis - October 3, 2020 Category: Molecular Biology Source Type: research

Characterization of a neutralizing anti-human galectin-1 monoclonal antibody with angioregulatory and immunomodulatory activities
AbstractGalectins, a family of highly conserved β-galactoside-binding proteins, control tumor progression by modulating different hallmarks of cancer. Galectin-1 (Gal-1), a proto-type member of this family, plays essential roles in tumor angiogenesis and immunosuppression by cross-linking glycosylated receptors on the surface of endothelial and immune cells. Targeted disruption of Gal-1 suppresses tumor growth by counteracting aberrant angiogenesis and reinforcing antitumor immunity in several experimental settings. Given the multiple therapeutic benefits associated with Gal-1 blockade, several Gal-1 inhibitors, inclu...
Source: Angiogenesis - September 30, 2020 Category: Molecular Biology Source Type: research

AgeR deletion decreases soluble fms-like tyrosine kinase 1 production and improves post-ischemic angiogenesis in uremic mice
AbstractPeripheral arterial disease occurs more frequently and has a worse prognosis in patients with chronic kidney disease (CKD). The receptor for advanced glycation end products (RAGE) is involved in multiple aspects of uremia-associated vasculopathy. Previous data suggest that the RAGE pathway may promote soluble fms-like tyrosine kinase 1 (sFlt1) production, an anti-angiogenic molecule. Thus, we tested the hypothesis that the deletion ofAgeR would decrease sFlt1 production and improve post-ischemic revascularization in uremic condition. We used a well-established CKD model (5/6 nephrectomy) in WT andAgeR−/&minus...
Source: Angiogenesis - September 22, 2020 Category: Molecular Biology Source Type: research

Angiogenic responses in a 3D micro-engineered environment of primary endothelial cells and pericytes
AbstractAngiogenesis plays a key role in the pathology of diseases such as cancer, diabetic retinopathy, and age-related macular degeneration. Understanding the driving forces of endothelial cell migration and organization, as well as the time frame of these processes, can elucidate mechanisms of action of important pathological pathways. Herein, we have developed an organ-specific microfluidic platform recapitulating the in vivo angiogenic microenvironment by co-culturing mouse primary brain endothelial cells with brain pericytes in a three-dimensional (3D) collagen scaffold. As a proof of concept, we show that this model...
Source: Angiogenesis - September 20, 2020 Category: Molecular Biology Source Type: research

A drug-tunable Flt23k gene therapy for controlled intervention in retinal neovascularization
AbstractGene therapies that chronically suppress vascular endothelial growth factor (VEGF) represent a new approach for managing retinal vascular leakage and neovascularization. However, constitutive suppression of VEGF in the eye may have deleterious side effects. Here, we developed a novel strategy to introduce Flt23k, a decoy receptor that binds intracellular VEGF, fused to the destabilizing domain (DD) ofEscherichia coli dihydrofolate reductase (DHFR) into the retina. The expressed DHFR(DD)-Flt23k fusion protein is degraded unless “switched on” by administering a stabilizer; in this case, the antibiotic tri...
Source: Angiogenesis - September 14, 2020 Category: Molecular Biology Source Type: research

RNA m6A methylation promotes the formation of vasculogenic mimicry in hepatocellular carcinoma via Hippo pathway
In conclusion, m6A methylation plays a key role in VM formation in HCC. METTL3 and YAP1 could be potential therapeutic targets via impairing VM formation in anti-metastatic strategies. (Source: Angiogenesis)
Source: Angiogenesis - September 12, 2020 Category: Molecular Biology Source Type: research

Epigenetic regulation of the lineage specificity of primary human dermal lymphatic and blood vascular endothelial cells
AbstractLymphatic and blood vascular endothelial cells (ECs) share several molecular and developmental features. However, these two cell types possess distinct phenotypic signatures, reflecting their different biological functions. Despite significant advances in elucidating how the specification of lymphatic and blood vascular ECs is regulated at the transcriptional level during development, the key molecular mechanisms governing their lineage identity under physiological or pathological conditions remain poorly understood. To explore the epigenomic signatures in the maintenance of EC lineage specificity, we compared the ...
Source: Angiogenesis - September 11, 2020 Category: Molecular Biology Source Type: research

Vascular PDGFR-alpha protects against BBB dysfunction after stroke in mice
AbstractBlood –brain barrier (BBB) dysfunction underlies the pathogenesis of many neurological diseases. Platelet-derived growth factor receptor-alpha (PDGFRα) induces hemorrhagic transformation (HT) downstream of tissue plasminogen activator in thrombolytic therapy of acute stroke. Thus, PDGFs are attractive therapeutic targets for BBB dysfunction. In the present study, we examined the role of PDGF signaling in the process of tissue remodeling after middle cerebral arterial occlusion (MCAO) in mice. Firstly, we found that imatinib increased lesion size after permanent MCAO in wild-type mice. Moreover, i matini...
Source: Angiogenesis - September 11, 2020 Category: Molecular Biology Source Type: research

Exacerbated inflammatory signaling underlies aberrant response to BMP9 in pulmonary arterial hypertension lung endothelial cells
In conclusion, our results show that the BMP9-induced aberrant EndMT in PAH pul monary ECs is dependent on exacerbated pro-inflammatory signaling mediated through IL6. (Source: Angiogenesis)
Source: Angiogenesis - August 18, 2020 Category: Molecular Biology Source Type: research

IQGAP1 causes choroidal neovascularization by sustaining VEGFR2-mediated Rac1 activation
AbstractLoss of visual acuity in neovascular age-related macular degeneration (nAMD) occurs when factors activate choroidal endothelial cells (CECs) to transmigrate the retinal pigment epithelium into the sensory retina and develop into choroidal neovascularization (CNV). Active Rac1 (Rac1GTP) is required for CEC migration and is induced by different AMD-related stresses, including vascular endothelial growth factor (VEGF). Besides its role in pathologic events, Rac1 also plays a role in physiologic functions. Therefore, we were interested in a method to inhibit pathologic activation of Rac1. We addressed the hypothesis th...
Source: Angiogenesis - August 10, 2020 Category: Molecular Biology Source Type: research

Leopold Auerbach ’s achievements in the field of vascular system
AbstractThe scientific activity of Leopold Auerbach (1828 –1897) was associated with Wrocław (Brelsau) medical school, which was renowned for brilliant descriptors of cardiovascular system, whose world-famous achievements became eponymous in history of medicine. Such terms as plexus myentericus Auerbach and Friedreich-Auerbach disease are still used wor ldwide. Little is known about the fact that the vascular system was at least as important in his scientific impact as neuromuscular field. Actually, one could realize that ganglion cells, which were previously discovered in cardiac location, were identified by Auerba...
Source: Angiogenesis - July 27, 2020 Category: Molecular Biology Source Type: research

Novel Murine Models of Cerebral Cavernous Malformations
AbstractCerebral cavernous malformations (CCMs) are ectatic capillary-venous malformations that develop in approximately 0.5% of the population. Patients with CCMs may develop headaches, focal neurologic deficits, seizures, and hemorrhages. While symptomatic CCMs, depending upon the anatomic location, can be surgically removed, there is currently no pharmaceutical therapy to treat CCMs. Several mouse models have been developed to better understand CCM pathogenesis and test therapeutics. The most common mouse models induce a large CCM burden that is anatomically restricted to the cerebellum and contributes to lethality in t...
Source: Angiogenesis - July 23, 2020 Category: Molecular Biology Source Type: research

Stromal cell-derived factor 1 (SDF1) attenuates platelet-derived growth factor-B (PDGF-B)-induced vascular remodeling for adipose tissue expansion in obesity
AbstractPlatelet-derived growth factor-B (PDGF-B) is a main factor to promote adipose tissue angiogenesis, which is responsible for the tissue expansion in obesity. In this process, PDGF-B induces the dissociation of pericytes from blood vessels; however, its regulatory mechanism remains unclear. In the present study, we found that stromal cell-derived factor 1 (SDF1) plays an essential role in this regulatory mechanism. SDF1 mRNA was increased in epididymal white adipose tissue (eWAT) of obese mice. Ex vivo pharmacological analyses using cultured adipose tissue demonstrated that physiological concentrations (1 –100&...
Source: Angiogenesis - July 21, 2020 Category: Molecular Biology Source Type: research

Excess centrosomes disrupt vascular lumenization and endothelial cell adherens junctions
AbstractProper blood vessel formation requires coordinated changes in endothelial cell polarity and rearrangement of cell –cell junctions to form a functional lumen. One important regulator of cell polarity is the centrosome, which acts as a microtubule organizing center. Excess centrosomes perturb aspects of endothelial cell polarity linked to migration, but whether centrosome number influences apical–basal polari ty and cell–cell junctions is unknown. Here, we show that excess centrosomes alter the apical–basal polarity of endothelial cells in angiogenic sprouts and disrupt endothelial cell–...
Source: Angiogenesis - July 21, 2020 Category: Molecular Biology Source Type: research

Are antiangiogenics a good ‘partner’ for immunotherapy in ovarian cancer?
AbstractOvarian cancer (OC) is associated with poor survival because there are a limited number of effective therapies. Two processes key to OC progression, angiogenesis and immune evasion, act synergistically to promote tumor progression. Tumor-associated angiogenesis promotes immune evasion, and tumor-related immune responses in the peritoneal cavity and tumor microenvironment (TME) affect neovascular formation. Therefore, suppressing the angiogenic pathways could facilitate the arrival of immune effector cells and reduce the presence of myeloid cells involved in immune suppression. To date, clinical studies have shown s...
Source: Angiogenesis - July 19, 2020 Category: Molecular Biology Source Type: research

Pleiotrophin selectively binds to vascular endothelial growth factor receptor 2 and inhibits or stimulates cell migration depending on α ν β 3 integrin expression
AbstractPleiotrophin (PTN) has a moderate stimulatory effect on endothelial cell migration through ανβ3 integrin, while it decreases the stimulatory effect of vascular endothelial growth factor A (VEGFA) and inhibits cell migration in the absence of ανβ3 through unknown mechanism(s). In the present work, by using a multitude of experimental approaches, we show that PTN binds to VEGF receptor type 2 (VEGFR2) with a KD of 11.6  nM. Molecular dynamics approach suggests that PTN binds to the same VEGFR2 region with VEGFA through its N-terminal domain. PTN inhibits phosphorylation of VEGFR2 at T...
Source: Angiogenesis - July 16, 2020 Category: Molecular Biology Source Type: research

Roxadustat (FG-4592) accelerates pulmonary growth, development, and function in a compensatory lung growth model
In this study, we evaluated the potential for Roxadustat (FG-4592), a prolyl hydroxylase inhibitor known to increase endogenous VEGF, in accelerating compensatory lung growth. Treatment with Roxadustat increased lung volume, total lung capacity, alveolarization, and exercise tolerance compared to controls following left pneumonectomy. However, this effect was likely modulated not only by increased VEGF, but rather also by decreased pigment epithelium-derived factor (PEDF), an anti-angiogenic factor. Furthermore, this mechanism of action may be specific to Roxadustat. Vadadustat (AKB-6548), a structurally similar prolyl hyd...
Source: Angiogenesis - July 13, 2020 Category: Molecular Biology Source Type: research

Embryonic circulating endothelial progenitor cells
AbstractThe development of vascular system in vertebrates has been traditionally explained by early vasculogenic assembly of angioblasts followed by angiogenic outgrowth of pre-existing vessels. The discovery of adult endothelial progenitor cells (Asahara et al. in Science 275(5302):964 –967, 1997) challenged this view, since postnatal vascular growth could be accomplished by recruitment of circulating cells with the ability to differentiate into endothelial cells. However, the existence of embryonic circulating endothelial progenitor cells and their actual contribution to vascul ar development is far less known. We ...
Source: Angiogenesis - June 30, 2020 Category: Molecular Biology Source Type: research

Arterial endoglin does not protect against arteriovenous malformations
ConclusionExpression of ENG is not required in arterial ECs to protect against AVM formation. (Source: Angiogenesis)
Source: Angiogenesis - June 5, 2020 Category: Molecular Biology Source Type: research

RHOQ is induced by DLL4 and regulates angiogenesis by determining the intracellular route of the Notch intracellular domain
We describe a new feed-forward mechanism regulating DLL4/Notch signalling, whereby RHOQ is induced by DLL4/Notch and is essential for the NICD nuclear translocation. In the absence of RHOQ, Notch1 becomes targeted for degradation in the autophagy pathway and NICD is sequestered from the nucleus and targeted for degradation in lysosomes. (Source: Angiogenesis)
Source: Angiogenesis - June 5, 2020 Category: Molecular Biology Source Type: research

Angiopoietin-2 as a marker of endothelial activation is a good predictor factor for intensive care unit admission of COVID-19 patients
ConclusionAngiopoietin-2 is a relevant predictive factor for ICU direct admission in COVID-19 patients. This result showing an endothelial activation reinforces the hypothesis of a COVID-19-associated microvascular dysfunction. (Source: Angiogenesis)
Source: Angiogenesis - May 26, 2020 Category: Molecular Biology Source Type: research

B-cell non-Hodgkin lymphoma: importance of angiogenesis and antiangiogenic therapy
AbstractAngiogenesis is critical for the initiation and progression of solid tumors, as well as hematological malignancies. While angiogenesis in solid tumors has been well characterized, a large body of investigation is devoted to clarify the impact of angiogenesis on lymphoma development. B-cell non-Hodgkin lymphoma (B-NHL) is the most common lymphoid malignancy with a highly heterogeneity. The malignancy remains incurable despite that the addition of rituximab to conventional chemotherapies provides substantial improvements. Several angiogenesis-related parameters, such as proangiogenic factors, circulating endothelial ...
Source: Angiogenesis - May 24, 2020 Category: Molecular Biology Source Type: research

Hedgehog signaling promotes angiogenesis directly and indirectly in pancreatic cancer
ConclusionInhibition of Hh signaling reduces tumor vascularity, suggesting that Hh plays a role in the maintenance or formation of the tumor vasculature. Whether the reduction in tumor growth and viability seen in the epithelium is a direct consequence of Hh pathway inhibition, or indirectly caused by its effect on the stroma and vasculature, remains to be evaluated. (Source: Angiogenesis)
Source: Angiogenesis - May 21, 2020 Category: Molecular Biology Source Type: research

Heterogeneity and chimerism of endothelial cells revealed by single-cell transcriptome in orthotopic liver tumors
AbstractThe liver is a common host organ for cancer, either through lesions that arise in liver epithelial cells [e.g., hepatocellular carcinoma (HCC)] or as a site of metastasis by tumors arising in other organs (e.g., colorectal cancer). However, the changes that occur in liver stromal cells in response to cancer have not been fully characterized, nor has it been determined whether the different sources of liver cancer induce distinct stromal changes. Here, we performed single-cell profiling of liver stromal cells from mouse models of induced spontaneous liver cancer or implanted colorectal liver metastases, with a focus...
Source: Angiogenesis - May 20, 2020 Category: Molecular Biology Source Type: research

Tumor-derived exosomes promote angiogenesis via adenosine A 2B receptor signaling
This study was performed to evaluate the role of adenosine receptors in TEX-induced angiogenesis.MethodsTEX produced by UMSCC47 head and neck cancer cell line were isolated by mini size exclusion chromatography (mini-SEC). Enzymatic activity of ectonucleotidases CD39/CD73 carried by TEX was measured by HPLC. Adenosine content of TEX was measured by UPLC –MS/MS. Primary human macrophages were co-incubated with TEX or exosomes derived from the plasma of head and neck cancer patients and their marker expression profile was analyzed by flow cytometry. The macrophage secretome was analyzed by angiogenesis arrays. The in v...
Source: Angiogenesis - May 17, 2020 Category: Molecular Biology Source Type: research

Endothelial deletion of ADAM10, a key regulator of Notch signaling, causes impaired decidualization and reduced fertility in female mice
AbstractDuring the initiation of pregnancy, the vasculature of the implantation site expands rapidly, yet little is known about this process or its role in fertility. Here, we report that endothelial-specific deletion of a disintegrin and metalloprotease 10 (ADAM10), an essential regulator of Notch signaling, results in severe subfertility in mice. We found that implantation sites develop until 5.5  days post conception (dpc) but are resorbed by 6.5 dpc inA10 ΔEC mice. Analysis of the mutant implantation sites showed impaired decidualization and abnormal vascular patterning compared to controls. Moreover, RNA-se...
Source: Angiogenesis - May 7, 2020 Category: Molecular Biology Source Type: research

Simultaneous fluorescence imaging of distinct nerve and blood vessel patterns in dual Thy1-YFP and Flt1-DsRed transgenic mice
In this study, dual fluorescence transgenic reporter mice were utilized to observe blood vessels and nervous tissues in organs postnatally. Thy1-YFP and Flt1-DsRed (TYFD) mice were interbred to achieve dual fluorescence in the offspring, with Thy1-YFP yellow fluorescence expressed primarily in nerves, and Flt1-DsRed fluorescence expressed selectively in blood vessels. Using this dual fluorescent mouse strain, we were able to visualize the networks of nervous and vascular tissue simultaneously in various organ systems both in the physiological state and after injury. Using ex vivo high-resolution imaging in this dual fluore...
Source: Angiogenesis - May 4, 2020 Category: Molecular Biology Source Type: research

Constitutively active PIK3CA mutations are expressed by lymphatic and vascular endothelial cells in capillary lymphatic venous malformation
In this study, we hypothesized that endothelial cells (EC) carry thePIK3CA mutations and play a major role in the cellular origin of CLVM. We isolated EC from the lesions of seven patients with CLVM and identifiedPIK3CA hotspot mutations. The CLVM EC exhibited constitutive phosphorylation of the PI3K effector AKT as well as hyperproliferation and increased resistance to cell death compared to normal EC. Inhibitors of PIK3CA (BYL719) and AKT (ARQ092) attenuated the proliferation of CLVM EC in a dose-dependent manner. A xenograft model of CLVM was developed by injecting patient-derived EC into the flanks of immunocompromised...
Source: Angiogenesis - April 29, 2020 Category: Molecular Biology Source Type: research

Apatinib as targeted therapy for advanced bone and soft tissue sarcoma: a dilemma of reversing multidrug resistance while suffering drug resistance itself
AbstractBone and soft tissue sarcomas are rare malignant tumors originated from mesenchymal tissues. They harbor more than 50 distinct subtypes and differ in pathological features and clinical courses. Despite the significant improvements in modern multi-modality treatment, the outcomes and overall survival rates remain poor for patients with advanced, refractory, metastatic, or relapsed diseases. The growth and metastasis of bone and soft tissue sarcoma largely depend on angiogenesis, and VEGF/VEGFR pathway is considered as the most prominent player in angiogenesis. Therefore, blockade of VEGF/VEGFR pathways is a promisin...
Source: Angiogenesis - April 23, 2020 Category: Molecular Biology Source Type: research

Lymphatic MAFB regulates vascular patterning during developmental and pathological lymphangiogenesis
AbstractMAFB is a transcription factor involved in the terminal differentiation of several cell types, including macrophages and keratinocytes. MAFB is also expressed in lymphatic endothelial cells (LECs) and is upregulated by VEGF-C/VEGFR-3 signaling. Recent studies have revealed that MAFB regulates several genes involved in lymphatic differentiation and that global Mafb knockout mice show defects in patterning of lymphatic vessels during embryogenesis. However, it has remained unknown whether this effect is LEC-intrinsic and whether MAFB might also be involved in postnatal lymphangiogenesis. We established conditional, l...
Source: Angiogenesis - April 18, 2020 Category: Molecular Biology Source Type: research

Raftlin is recruited by neuropilin-1 to the activated VEGFR2 complex to control proangiogenic signaling
ConclusionNrp1 is an important co-receptor for VEGFR2; however, its functions are still only partially understood. We show that raftlin works with Nrp1 in endothelial cells to control intracellular trafficking of the activated VEGFR2. This modulates the response to VEGF and controls endothelial cell migration. (Source: Angiogenesis)
Source: Angiogenesis - April 8, 2020 Category: Molecular Biology Source Type: research

New insights into the role of mitochondria in cardiac microvascular ischemia/reperfusion injury
AbstractAs reperfusion therapies have become more widely used in acute myocardial infarction patients, ischemia-induced myocardial damage has been markedly reduced, but reperfusion-induced cardiac injury has become increasingly evident. The features of cardiac ischemia –reperfusion (I/R) injury include microvascular perfusion defects, platelet activation and sequential cardiomyocyte death due to additional ischemic events at the reperfusion stage. Microvascular obstruction, defined as a no-reflow phenomenon, determines the infarct zone, myocardial function and p eri-operative mortality. Cardiac microvascular endothel...
Source: Angiogenesis - April 2, 2020 Category: Molecular Biology Source Type: research

Angiostatic effects of ascorbic acid: current status and future perspectives
AbstractAnti-angiogenesis effect of ascorbic acid (AA) is still controversial. However, most of the scientific evidence suggests that AA has anti-angiogenesis effects on a number of test systems, including laboratory animals, human beings, and their derived cell lines. The information provided in this paper suggests that AA may be a hopeful angiostatic agent for the treatment of cancer. (Source: Angiogenesis)
Source: Angiogenesis - April 1, 2020 Category: Molecular Biology Source Type: research