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Gregory Farber, Matthew M Parks, Nicole Lustgarten Guahmich, Yi Zhang, Sébastien Monette, Scott C Blanchard, Annarita Di Lorenzo, Carl P Blobel
The coronary vasculature is crucial for normal heart function, yet much remains to be learned about its development, especially the maturation of coronary arterial endothelium. Here, we show that endothelial inactivation of ADAM10, a key regulator of Notch signaling, leads to defects in coronary arterial differentiation, as evidenced by dysregulated genes related to Notch signaling and arterial identity. Moreover, transcriptome analysis indicated reduced EGFR signaling in A10ΔEC coronary endothelium. Further analysis revealed that A10ΔEC mice have enlarged dysfunctional hearts with abnormal myocardial compaction, and increased expression of venous and immature endothelium markers...
November 16, 2018: Angiogenesis
Moran Zarfati, Irit Avivi, Benjamin Brenner, Tami Katz, Anat Aharon
Bone marrow microenvironment is known to support angiogenesis, thus contributing to progression of multiple myeloma (MM). Bortezomib, a proteasome inhibitor (PI) widely used in MM treatment, has anti-angiogenic activity. Extracellular vesicles (EVs), shedding from cell surface, serve as mediators in cell-to-cell communication. We have hypothesized that MM cells (MMCs) treated with bortezomib generate EVs that could diminish angiogenesis, thus limiting MM progression. In the present study, EVs were obtained from MMCs (RPMI-8226), untreated (naïve) or pre-treated with bortezomib...
November 1, 2018: Angiogenesis
Javier A Montoya-Zegarra, Erica Russo, Peter Runge, Maria Jadhav, Ann-Helen Willrodt, Szymon Stoma, Simon F Nørrelykke, Michael Detmar, Cornelia Halin
Due to their involvement in many physiologic and pathologic processes, there is a great interest in identifying new molecular pathways that mediate the formation and function of blood and lymphatic vessels. Vascular research increasingly involves the image-based analysis and quantification of vessel networks in tissue whole-mounts or of tube-like structures formed by cultured endothelial cells in vitro. While both types of experiments deliver important mechanistic insights into (lymph)angiogenic processes, the manual analysis and quantification of such experiments are typically labour-intensive and affected by inter-experimenter variability...
October 28, 2018: Angiogenesis
Siamack Sabrkhany, Marijke J E Kuijpers, Arjan W Griffioen, Mirjam G A Oude Egbrink
We would like to promote the fact that platelets are increasingly emerging as a rich source of potential biomarkers for cancer. Blood platelets contain vast amounts of bioactive proteins, such as growth factors, chemokines, and cytokines. These proteins are either synthesized by the megakaryocytes that produce the platelets or are sequestered by the circulating platelets from the blood, in which case these proteins may originate from the tumor. Recent studies in patients have demonstrated that the presence of cancer influences multiple platelet characteristics (e...
October 20, 2018: Angiogenesis
Sonia L Hernandez, Mildred Nelson, Georgia R Sampedro, Naina Bagrodia, Ann M Defnet, Bianca Lec, Jared Emolo, Rebecca Kirschner, Lydia Wu, Henry Biermann, Stephanie Shen, Juliane Bubeck Wardenburg, Jessica J Kandel
Staphylococcus aureus infection is one of the leading causes of morbidity in hospitalized patients in the United States, an effect compounded by increasing antibiotic resistance. The secreted agent hemolysin alpha toxin (Hla) requires the receptor A Disintegrin And Metalloproteinase domain-containing protein 10 (ADAM10) to mediate its toxic effects. We hypothesized that these effects are in part regulated by Notch signaling, for which ADAM10 activation is essential. Notch proteins function in developmental and pathological angiogenesis via the modulation of key pathways in endothelial and perivascular cells...
October 15, 2018: Angiogenesis
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
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...
November 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...
November 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...
November 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...
November 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...
November 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...
November 2018: Angiogenesis
Marchien G Dallinga, Bahar Yetkin-Arik, Richelle P Kayser, Ilse M C Vogels, Patrycja Nowak-Sliwinska, Arjan W Griffioen, Cornelis J F van Noorden, Ingeborg Klaassen, Reinier O Schlingemann
Tip cells, the leading cells of angiogenic sprouts, were identified in cultures of human umbilical vein endothelial cells (HUVECs) by using CD34 as a marker. Here, we show that tip cells are also present in primary human microvascular endothelial cells (hMVECs), a more relevant endothelial cell type for angiogenesis. By means of flow cytometry, immunocytochemistry, and qPCR, it is shown that endothelial cell cultures contain a dynamic population of CD34+ cells with many hallmarks of tip cells, including filopodia-like extensions, elevated mRNA levels of known tip cell genes, and responsiveness to stimulation with VEGF and inhibition by DLL4...
November 2018: Angiogenesis
Aaron B Simmons, Colin A Bretz, Haibo Wang, Eric Kunz, Kassem Hajj, Carson Kennedy, Zhihong Yang, Thipparat Suwanmanee, Tal Kafri, M Elizabeth Hartnett
The article "Gene therapy knockdown of VEGFR2 in retinal endothelial cells to treat retinopathy", written by "Aaron B. Simmons, Colin A. Bretz, Haibo Wang, Eric Kunz, Kassem Hajj, Carson Kennedy, Zhihong Yang, Thipparat Suwanmanee, Tal Kafri and M. Elizabeth Hartnett", was originally published electronically on the publisher's internet portal (currently SpringerLink) on 05 May 2018 without open access. With the author(s)' decision to opt for Open Choice the copyright of the article changed on 20 June 2018 to © The Author(s) 2018 and the article is forthwith distributed under the terms of the Creative Commons Attribution 4...
November 2018: Angiogenesis
Lingyan Zhu, Jixiong Xu, Ying Liu, Tian Gong, Jianying Liu, Qiong Huang, Shane Fischbach, Wenquan Zou, Xiangwei Xiao
Diabetic retinopathy (DR), a major complication of diabetes caused by vascular damage and pathological proliferation of retinal vessels, often progresses to vision loss. Vascular endothelial growth factor (VEGF) signaling plays a pivotal role in the development of DR, but the exact underlying molecular mechanisms remain ill-defined. Cellular prion protein (PrPc ) is a surface protein expressed by vascular endothelial cells, and the increased expression of PrPc is associated with physiological and pathological vascularization...
November 2018: Angiogenesis
Maarten M Brandt, Christian G M van Dijk, Ihsan Chrifi, Heleen M Kool, Petra E Bürgisser, Laura Louzao-Martinez, Jiayi Pei, Robbert J Rottier, Marianne C Verhaar, Dirk J Duncker, Caroline Cheng
AIMS: Formation of a functional vascular system is essential and its formation is a highly regulated process initiated during embryogenesis, which continues to play important roles throughout life in both health and disease. In previous studies, Fzd5 was shown to be critically involved in this process and here we investigated the molecular mechanism by which endothelial loss of this receptor attenuates angiogenesis. METHODS AND RESULTS: Using short interference RNA-mediated loss-of-function assays, the function and mechanism of signaling via Fzd5 was studied in human endothelial cells (ECs)...
November 2018: Angiogenesis
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