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Jordan Darden, Laura Beth Payne, Huaning Zhao, John C Chappell
Pericyte investment into new blood vessels is essential for vascular development such that mis-regulation within this phase of vessel formation can contribute to numerous pathologies including arteriovenous and cerebrovascular malformations. It is critical therefore to illuminate how angiogenic signaling pathways intersect to regulate pericyte migration and investment. Here, we disrupted vascular endothelial growth factor-A (VEGF-A) signaling in ex vivo and in vitro models of sprouting angiogenesis, and found pericyte coverage to be compromised during VEGF-A perturbations...
September 20, 2018: Angiogenesis
Marie E Faughnan, James R Gossage, Murali M Chakinala, S Paul Oh, Raj Kasthuri, Christopher C W Hughes, Justin P McWilliams, Joseph G Parambil, Nicholas Vozoris, Jill Donaldson, Gitanjali Paul, Pamela Berry, Dennis L Sprecher
Pazopanib (Votrient) is an orally administered tyrosine kinase inhibitor that blocks VEGF receptors potentially serving as anti-angiogenic treatment for hereditary hemorrhagic telangiectasia (HHT). We report a prospective, multi-center, open-label, dose-escalating study [50 mg, 100 mg, 200 mg, and 400 mg], designed as a proof-of-concept study to demonstrate efficacy of pazopanib on HHT-related bleeding, and to measure safety. Patients, recruited at 5 HHT Centers, required ≥ 2 Curacao criteria AND [anemia OR severe epistaxis with iron deficiency]...
September 6, 2018: Angiogenesis
V van Duinen, D Zhu, C Ramakers, A J van Zonneveld, P Vulto, T Hankemeier
Angiogenic sprouting, the growth of new blood vessels from pre-existing vessels, is orchestrated by cues from within the cellular microenvironment, such as biochemical gradients and perfusion. However, many of these cues are missing in current in vitro models of angiogenic sprouting. We here describe an in vitro platform that integrates both perfusion and the generation of stable biomolecular gradients and demonstrate its potential to study more physiologically relevant angiogenic sprouting and microvascular stabilization...
August 31, 2018: Angiogenesis
Marco Rusnati, Patrizia Borsotti, Elisabetta Moroni, Chiara Foglieni, Paola Chiodelli, Laura Carminati, Denise Pinessi, Douglas S Annis, Giulia Paiardi, Antonella Bugatti, Alessandro Gori, Renato Longhi, Dorina Belotti, Deane F Mosher, Giorgio Colombo, Giulia Taraboletti
Thrombospondin (TSP)-1 and TSP-2 share similar structures and functions, including a remarkable antiangiogenic activity. We have previously demonstrated that a mechanism of the antiangiogenic activity of TSP-1 is the interaction of its type III repeats domain with fibroblast growth factor-2 (FGF2), affecting the growth factor bioavailability and angiogenic activity. Since the type III repeats domain is conserved in TSP-2, this study aimed at investigating whether also TSP-2 retained the ability to interact with FGF2...
August 30, 2018: Angiogenesis
Cecilia Higgs, Yanick J Crow, Denise M Adams, Emmanuel Chang, Don Hayes, Utz Herbig, James N Huang, Ryan Himes, Kunal Jajoo, F Brad Johnson, Susan D Reynolds, Yoshihiro Yonekawa, Mary Armanios, Farid Boulad, Courtney D DiNardo, Carlo Dufour, Frederick D Goldman, Shakila Khan, Christian Kratz, Kasiani C Myers, Ganesh Raghu, Blanche P Alter, Geraldine Aubert, Sonia Bhala, Edward W Cowen, Yigal Dror, Mounif El-Youssef, Bruce Friedman, Neelam Giri, Lisa Helms Guba, Payal P Khincha, Tiffany F Lin, Hilary Longhurst, Lisa J McReynolds, Adam Nelson, Tim Olson, Anne Pariser, Rosario Perona, Ghadir Sasa, Kristen Schratz, Douglas A Simonetto, Danielle Townsley, Michael Walsh, Katherine Stevens, Suneet Agarwal, Alison A Bertuch, Sharon A Savage
Vascular complications such as bleeding due to gastrointestinal telangiectatic anomalies, pulmonary arteriovenous malformations, hepatopulmonary syndrome, and retinal vessel abnormalities are being reported in patients with telomere biology disorders (TBDs) more frequently than previously described. The international clinical care consortium of telomere-associated ailments and family support group Dyskeratosis Congenita Outreach, Inc. held a workshop on vascular abnormalities in the TBDs at the National Cancer Institute in October 2017...
August 25, 2018: Angiogenesis
Shuo Li, Hua-Xiang Xu, Chun-Tao Wu, Wen-Quan Wang, Wei Jin, He-Li Gao, Hao Li, Shi-Rong Zhang, Jin-Zhi Xu, Zi-Hao Qi, Quan-Xing Ni, Xian-Jun Yu, Liang Liu
Pancreatic cancer is one of the most lethal malignancies worldwide. Although the standard of care in pancreatic cancer has improved, prognoses for patients remain poor with a 5-year survival rate of < 5%. Angiogenesis, namely, the formation of new blood vessels from pre-existing vessels, is an important event in tumor growth and hematogenous metastasis. It is a dynamic and complex process involving multiple mechanisms and is regulated by various molecules. Inhibition of angiogenesis has been an established therapeutic strategy for many solid tumors...
August 24, 2018: Angiogenesis
Matteo Bocci, Jonas Sjölund, Ewa Kurzejamska, David Lindgren, Nour-Al-Dain Marzouka, Michael Bartoschek, Mattias Höglund, Kristian Pietras
Cancer cells sustain their metabolic needs through nutrients and oxygen supplied by the bloodstream. The requirement for tumor angiogenesis has been therapeutically exploited in the clinical setting mainly by means of inhibition of the vascular endothelial growth factor family of ligands and receptors. Despite promising results in preclinical models, the benefits for patients proved to be limited. Inadequate efficacy similarly halted the development of agents impinging on the activity of the activin receptor-like kinase (ALK)1, a member of the transforming growth factor-β superfamily...
August 21, 2018: Angiogenesis
Emmanuel Nwadozi, Andrew Ng, Anna Strömberg, Hsin-Yi Liu, Karl Olsson, Thomas Gustafsson, Tara L Haas
Skeletal muscle capillarity is characteristically reduced in mature leptin receptor-deficient (Leprdb ) mice, which has been attributed to the capillary loss that occurs secondary to metabolic dysfunction. Despite wide recognition of leptin as a pro-angiogenic molecule, the contribution of this adipokine has largely been overlooked in peripheral tissues. Moreover, prior documentation of leptin production within skeletal muscle indicates a potential paracrine role in maintaining local tissue homeostasis. Thus, we hypothesized that leptin is a physiological local paracrine regulator of skeletal muscle angiogenesis and that its production may be modulated by nutrient availability...
August 18, 2018: Angiogenesis
Ihsan Chrifi, Laura Louzao-Martinez, Maarten M Brandt, Christian G M van Dijk, Petra E Bürgisser, Changbin Zhu, Johan M Kros, Marianne C Verhaar, Dirk J Duncker, Caroline Cheng
Vascular endothelial (VE) cadherin is a key component of endothelial adherens junctions (AJs) and plays an important role in maintaining vascular integrity. Endocytosis of VE-cadherin regulates junctional strength and a decrease of surface VE-cadherin reduces vascular stability. However, disruption of AJs is also a requirement for vascular sprouting. Identifying novel regulators of endothelial endocytosis could enhance our understanding of angiogenesis. Here, we evaluated the angiogenic potential of (CKLF-like MARVEL transmembrane domain 4) CMTM4 and assessed in which molecular pathway CMTM4 is involved during angiogenesis...
August 10, 2018: Angiogenesis
Shirley Man, Gonzalo Sanchez Duffhues, Peter Ten Dijke, David Baker
Endothelial cells (ECs) have been found to be capable of acquiring a mesenchymal phenotype through a process known as endothelial-to-mesenchymal transition (EndMT). First seen in the developing embryo, EndMT can be triggered postnatally under certain pathological conditions. During this process, ECs dedifferentiate into mesenchymal stem-like cells (MSCs) and subsequently give rise to cell types belonging to the mesoderm lineage. As EndMT contributes to a multitude of diseases, pharmacological modulation of the signaling pathways underlying EndMT may prove to be effective as a therapeutic treatment...
August 3, 2018: Angiogenesis
Petra Wolint, Annina Bopp, Anna Woloszyk, Yinghua Tian, Olivera Evrova, Monika Hilbe, Pietro Giovanoli, Maurizio Calcagni, Simon P Hoerstrup, Johanna Buschmann, Maximilian Y Emmert
While cell therapy has been proposed as next-generation therapy to treat the diseased heart, current strategies display only limited clinical efficacy. Besides the ongoing quest for the ideal cell type, in particular the very low retention rate of single-cell (SC) suspensions after delivery remains a major problem. To improve cellular retention, cellular self-assembly into 3D microtissues (MTs) prior to transplantation has emerged as an encouraging alternative. Importantly, 3D-MTs have also been reported to enhance the angiogenic activity and neovascularization potential of stem cells...
July 16, 2018: Angiogenesis
R Gianni-Barrera, A Butschkau, A Uccelli, A Certelli, P Valente, M Bartolomeo, E Groppa, M G Burger, R Hlushchuk, M Heberer, D J Schaefer, L Gürke, V Djonov, B Vollmar, A Banfi
VEGF induces normal or aberrant angiogenesis depending on its dose in the microenvironment around each producing cell in vivo. This transition depends on the balance between VEGF-induced endothelial stimulation and PDGF-BB-mediated pericyte recruitment, and co-expression of PDGF-BB normalizes aberrant angiogenesis despite high VEGF doses. We recently found that VEGF over-expression induces angiogenesis in skeletal muscle through an initial circumferential vascular enlargement followed by longitudinal splitting, rather than sprouting...
July 16, 2018: Angiogenesis
Anita Virtanen, Outi Huttala, Kati Tihtonen, Tarja Toimela, Tuula Heinonen, Jukka Uotila
OBJECTIVE: The purpose of the study was to determine the angiogenic capacity of sera in early and late pregnancy and in umbilical blood serum after childbirth, and to define how angiogenic properties assessed in a functional in vitro test are related to individual angiogenic proteins in six women with pre-eclampsia and in six healthy pregnant controls. METHODS: Maternal first and third trimester serum samples, and umbilical blood samples after childbirth, were tested in an in vitro human adipose stromal cell-human umbilical vein endothelial cell (hASC-HUVEC) vasculogenesis/angiogenesis assay...
July 12, 2018: Angiogenesis
Christian Uhl, Moritz Markel, Thomas Broggini, Melina Nieminen, Irina Kremenetskaia, Peter Vajkoczy, Marcus Czabanka
INTRODUCTION: Alterations in vascular morphogenesis are hallmarks of antiangiogenesis-resistant tumor vessels. Vascular morphogenesis is regulated by ephrinB2-EphB4 system which may induce different biological effects depending on the oncological and molecular contexts. It was the aim of the current study to characterize the influence of EphB4 on tumor microcirculation after antiangiogenic treatment using different SF126 glioma models. MATERIALS AND METHODS: Using an ecotropic transfection system, empty vector (pLXSN) or EphB4 (EphB4OE ) overexpressing Phoenix-ECO cells were coimplanted with SF126 glioma cells subcutaneously (dorsal skinfold chamber, DSC) and orthotopically (cranial window, CW)...
July 10, 2018: Angiogenesis
Ting-Ting Chang, Liang-Yu Lin, Jaw-Wen Chen
Systemic inflammation might contribute to the impairment of neovasculogenesis and endothelial progenitor cell (EPC) function in clinical diabetes mellitus (DM). Macrophage inflammatory protein-1β (MIP-1β) is an inflammatory chemokine that may be up-regulated in clinical DM. Its role in diabetic vasculopathy was not clarified. This study aimed to investigate the role of MIP-1β in human EPCs and in neovasculogenesis in different diabetic animal models with hindlimb ischemia. EPCs chamber assay and in vitro tube formation assay were used to estimate the degree of EPC migration and tube formation abilities...
July 9, 2018: Angiogenesis
Susan J Doh, Michael Yamakawa, Samuel M Santosa, Mario Montana, Kai Guo, Joseph R Sauer, Nicholas Curran, Kyu-Yeon Han, Charles Yu, Masatsugu Ema, Mark I Rosenblatt, Jin-Hong Chang, Dimitri T Azar
The study of lymphangiogenesis is an emerging science that has revealed the lymphatic system as a central player in many pathological conditions including cancer metastasis, lymphedema, and organ graft rejection. A thorough understanding of the mechanisms of lymphatic growth will play a key role in the development of therapeutic strategies against these conditions. Despite the known potential of this field, the study of lymphatics has historically lagged behind that of hemangiogenesis. Until recently, significant strides in lymphatic studies were impeded by a lack of lymphatic-specific markers and suitable experimental models compared to those of the more immediately visible blood vasculature...
July 3, 2018: Angiogenesis
Soheila Zeinali, Colette A Bichsel, Nina Hobi, Manuela Funke, Thomas M Marti, Ralph A Schmid, Olivier T Guenat, Thomas Geiser
Idiopathic pulmonary fibrosis is characterized by a progressive scarring and stiffening of the peripheral lung tissue that decreases lung function. Over the course of the disease, the lung microvasculature undergoes extensive remodeling. There is increased angiogenesis around fibrotic foci and an absence of microvessels within the foci. To elucidate how the anti-fibrotic drug nintedanib acts on vascular remodeling, we used an in vitro model of perfusable microvessels made with primary endothelial cells and primary lung fibroblasts in a microfluidic chip...
July 2, 2018: Angiogenesis
Huichun Liang, Fei Ge, Yuhui Xu, Ji Xiao, Zhongmei Zhou, Rong Liu, Ceshi Chen
The sprouting of endothelial cells is the first step of tumor angiogenesis. Our previous study suggests that miR-153 suppresses breast tumor angiogenesis partially through targeting hypoxia-induced factor (HIF1α). In this study, we demonstrated that miR-153 also suppresses the migration and the tube formation of endothelial cells through directly targeting angiopoietin 1 (ANG1) in breast cancer cells. There was a negative correlation between miR-153 and ANG1 levels in breast cancer. miR-153 blocked the expression and secretion of ANG1 in breast cancer cells through binding to ANG1 mRNA...
June 29, 2018: Angiogenesis
Devika Kir, Erica Schnettler, Shrey Modi, Sundaram Ramakrishnan
Non-coding RNAs are functional RNA molecules comprising the majority of human transcriptome. Only about 1.5% of the human genome is transcribed into messenger RNAs (mRNA) that are translated into proteins. Among the non-coding RNAs, miRNAs are extensively studied and miR targets in endothelial cells, perivascular cells, and angiogenic signaling are relatively well defined. MicroRNAs not only regulate transcripts in situ but also function as paracrine mediators in affecting angiogenesis at distant sites. Exosomal miRs are implicated in modulating endothelial cell function and angiogenesis...
June 28, 2018: Angiogenesis
Duy T Dao, Lorenzo Anez-Bustillos, Jared Ourieff, Amy Pan, Paul D Mitchell, Hiroko Kishikawa, Gillian L Fell, Meredith A Baker, Randolph S Watnick, Hong Chen, Thomas E Hamilton, Michael S Rogers, Diane R Bielenberg, Mark Puder
Children with hypoplastic lung diseases, such as congenital diaphragmatic hernia, can require life support via extracorporeal membrane oxygenation and systemic anticoagulation, usually in the form of heparin. The role of heparin in angiogenesis and organ growth is inconclusive, with conflicting data reported in the literature. This study aimed to investigate the effects of heparin on lung growth in a model of compensatory lung growth (CLG). Compared to the absence of heparin, treatment with heparin decreased the vascular endothelial growth factor (VEGF)-mediated activation of VEGFR2 and mitogenic effect on human lung microvascular endothelial cells in vitro...
June 28, 2018: Angiogenesis
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