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https://www.readbyqxmd.com/read/29352118/pi3k-mtor-inhibition-promotes-the-regression-of-experimental-vascular-malformations-driven-by-pik3ca-activating-mutations
#1
Laura di Blasio, Alberto Puliafito, Paolo Armando Gagliardi, Valentina Comunanza, Desiana Somale, Giulia Chiaverina, Federico Bussolino, Luca Primo
Somatic activating mutations within the PIK3CA gene have been recently detected in sporadic lymphatic and venous malformations, and in vascular malformations (VM) associated to overgrowth syndromes, such as CLOVES and Klippel-Trenaunay syndrome. Although VM are often limited to specific tissue areas and can be well treated, in extended or recurrent lesions novel therapeutic approaches are needed. We generated a mouse model of VM by local expression of PIK3CA-activating mutation in endothelial cells. PIK3CA-driven lesions are characterized by large areas of hemorrhage, hyperplastic vessels, infiltrates of inflammatory cells, and elevated endothelial cell density...
January 19, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29332242/selective-ikk2-inhibitor-imd0354-disrupts-nf-%C3%AE%C2%BAb-signaling-to-suppress-corneal-inflammation-and-angiogenesis
#2
Anton Lennikov, Pierfrancesco Mirabelli, Anthony Mukwaya, Mira Schaupper, Muthukumar Thangavelu, Mieszko Lachota, Zaheer Ali, Lasse Jensen, Neil Lagali
Corneal neovascularization is a sight-threatening condition caused by angiogenesis in the normally avascular cornea. Neovascularization of the cornea is often associated with an inflammatory response, thus targeting VEGF-A alone yields only a limited efficacy. The NF-κB signaling pathway plays important roles in inflammation and angiogenesis. Here, we study consequences of the inhibition of NF-κB activation through selective blockade of the IKK complex IκB kinase β (IKK2) using the compound IMD0354, focusing on the effects of inflammation and pathological angiogenesis in the cornea...
January 13, 2018: Angiogenesis
https://www.readbyqxmd.com/read/29329415/establishment-of-a-three-dimensional-model-to-study-human-uterine-angiogenesis
#3
Camille L Duran, Colette A Abbey, Kayla J Bayless
STUDY QUESTION: Can primary human uterine microvascular endothelial cells (UtMVECs) be used as a model to study uterine angiogenic responses in vitro that are relevant in pregnancy? SUMMARY ANSWER: UtMVECs demonstrated angiogenic responses when stimulated with proangiogenic factors, including sphingosine 1-phosphate (S1P), vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), physiological levels of wall shear stress (WSS), human chorionic gonadotropin (hCG) and various combinations of estrogen and progesterone...
December 21, 2017: Molecular Human Reproduction
https://www.readbyqxmd.com/read/29320922/co-emergence-of-specialized-endothelial-cells-from-embryonic-stem-cells
#4
Nicole Madfis, Zhiqiang Lin, Ashwath Kumar, Simone A Douglas, Manu O Platt, Yuhong Fan, Kara E McCloskey
A well-formed and robust vasculature is critical to the health of most organ systems in the body. However, the endothelial cells (ECs) forming the vasculature can exhibit a number of distinct functional subphenotypes like arterial or venous ECs, as well as angiogenic tip and stalk ECs. Here, we investigate the in vitro differentiation of EC subphenotypes from embryonic stem cells (ESCs) using. Using our staged induction methods and chemically-defined mediums, highly angiogenic EC subpopulations, as well as, less proliferative and less migratory EC subpopulations are derived...
January 10, 2018: Stem Cells and Development
https://www.readbyqxmd.com/read/29291009/mir-93-5p-enhances-growth-and-angiogenesis-capacity-of-huvecs-by-down-regulating-eplin
#5
Liang Liang, Lei Zhao, Ying Zan, Qing Zhu, Juan Ren, Xinhan Zhao
Tumor angiogenesis is essential in delivering oxygen and nutrients to growing tumors, and therefore considered as a hallmark of cancer. MicroRNAs (miRNAs) have been shown to play important roles in regulating tumor angiogenesis. MicroRNA-93-5p (miR-93-5p) has been identified as an oncogenic miRNA in a variety of human malignancies and involved in tumor angiogenesis in astrocytoma. However, the direct effect(s) of miR-93-5p on the biological behaviors of endothelial cells have not been investigated. Thus, in the present study we investigated the role(s) of miR-93-5p in regulating the functions of human umbilical vein endothelial cells (HUVECs)...
December 5, 2017: Oncotarget
https://www.readbyqxmd.com/read/29290798/ultrasound-molecular-imaging-of-vegfr-2-in-clear-cell-renal-cell-carcinoma-tracks-disease-response-to-antiangiogenic-and-notch-inhibition-therapy
#6
Juan D Rojas, Fanglue Lin, Yun-Chen Chiang, Anna Chytil, Diana C Chong, Victoria L Bautch, W Kimryn Rathmell, Paul A Dayton
Metastatic clear-cell renal cell carcinoma (ccRCC) affects thousands of patients worldwide each year. Antiangiogenic therapy has been shown to have beneficial effects initially, but resistance is eventually developed. Therefore, it is important to accurately track the response of cancer to different therapeutics in order to appropriately adjust the therapy to maximize efficacy. Change in tumor volume is the current gold standard for determining efficacy of treatment. However, functional variations can occur much earlier than measurable volume changes...
2018: Theranostics
https://www.readbyqxmd.com/read/29289530/a-vascular-endothelial-growth-factor-dependent-sprouting-angiogenesis-assay-based-on-an-in-vitro-human-blood-vessel-model-for-the-study-of-anti-angiogenic-drugs
#7
Joris Pauty, Ryo Usuba, Irene Gayi Cheng, Louise Hespel, Haruko Takahashi, Keisuke Kato, Masayoshi Kobayashi, Hiroyuki Nakajima, Eujin Lee, Florian Yger, Fabrice Soncin, Yukiko T Matsunaga
Angiogenesis is the formation of new capillaries from pre-existing blood vessels and participates in proper vasculature development. In pathological conditions such as cancer, abnormal angiogenesis takes place. Angiogenesis is primarily carried out by endothelial cells, the innermost layer of blood vessels. The vascular endothelial growth factor-A (VEGF-A) and its receptor-2 (VEGFR-2) trigger most of the mechanisms activating and regulating angiogenesis, and have been the targets for the development of drugs...
December 20, 2017: EBioMedicine
https://www.readbyqxmd.com/read/29283055/the-role-of-angiogenesis-in-coronary-artery-disease-a-double-edged-sword-intraplaque-angiogenesis-in-physiopathology-and-therapeutic-angiogenesis-for-treatment
#8
Wen Wu, Xiaobo Li, Guangfeng Zuo, Jiangqin Pu, Xinlei Wu, Shaoliang Chen
Angiogenesis is described as a sprouting and growth process of new blood vessels from pre-existing vasculature. The relationship between angiogenesis and coronary artery disease (CAD) is double-sided. On one hand, angiogenesis within plaques is responsible for facilitating the growth and vulnerability of plaques by causing intraplaque hemorrhage and inflammatory cell influx, and overabundance of erythrocytes and inflammatory cells within a plaque probably causes plaque rupture, further leading to acute coronary syndrome...
December 27, 2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/29226860/a-hybrid-multiscale-model-for-investigating-tumor-angiogenesis-and-its-response-to%C3%A2-cell-based-therapy
#9
Melisa Hendrata, Janti Sudiono
Angiogenesis, a formation of blood vessels from an existing vasculature, plays a key role in tumor growth and its progression into cancer. The lining of blood vessels consists of endothelial cells (ECs) which proliferate and migrate, allowing the capillaries to sprout towards the tumor to deliver the needed oxygen. Various treatments aiming to suppress or even inhibit angiogenesis have been explored. Mesenchymal stem cells (MSCs) have recently been undergoing development in cell-based therapy for cancer due to their ability to migrate towards the capillaries and induce the apoptosis of the ECs, causing capillary degeneration...
December 5, 2017: In Silico Biology
https://www.readbyqxmd.com/read/29226547/avian-embryonic-coronary-arterio-venous-pattering-involves-the-contribution-of-different-endothelial-and-endocardial-cell-populations
#10
Paul Palmquist-Gomes, Juan Antonio Guadix, José M Pérez-Pomares
BACKGROUND: Coronary vasculature irrigates the myocardium and is crucial to late embryonic and adult heart function. Despite the developmental significance and clinical relevance of these blood vessels, the embryonic origin and the cellular and molecular mechanisms that regulate coronary arterio-venous patterning are not known in detail. In this study, we have used the avian embryo to dissect the ontogenetic origin and morphogenesis of coronary vasculature. RESULTS: We show that sinus venosus endocardial sprouts and proepicardial angioblasts pioneer coronary vascular formation, invading the developing heart simultaneously...
December 11, 2017: Developmental Dynamics: An Official Publication of the American Association of Anatomists
https://www.readbyqxmd.com/read/29214994/human-liver-segments-role-of-cryptic-liver-lobes-and-vascular-physiology-in-the-development-of-liver-veins-and-left-right-asymmetry
#11
Jill P J M Hikspoors, Mathijs M J P Peeters, Nutmethee Kruepunga, Hayelom K Mekonen, Greet M C Mommen, S Eleonore Köhler, Wouter H Lamers
Couinaud based his well-known subdivision of the liver into (surgical) segments on the branching order of portal veins and the location of hepatic veins. However, both segment boundaries and number remain controversial due to an incomplete understanding of the role of liver lobes and vascular physiology on hepatic venous development. Human embryonic livers (5-10 weeks of development) were visualized with Amira 3D-reconstruction and Cinema 4D-remodeling software. Starting at 5 weeks, the portal and umbilical veins sprouted portal-vein branches that, at 6...
December 7, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29202457/recapitulation-of-developmental-mechanisms-to-revascularize-the-ischemic-heart
#12
Karina N Dubé, Tonia M Thomas, Sonali Munshaw, Mala Rohling, Paul R Riley, Nicola Smart
Restoring blood flow after myocardial infarction (MI) is essential for survival of existing and newly regenerated tissue. Endogenous vascular repair processes are deployed following injury but are poorly understood. We sought to determine whether developmental mechanisms of coronary vessel formation are intrinsically reactivated in the adult mouse after MI. Using pulse-chase genetic lineage tracing, we establish that de novo vessel formation constitutes a substantial component of the neovascular response, with apparent cellular contributions from the endocardium and coronary sinus...
November 16, 2017: JCI Insight
https://www.readbyqxmd.com/read/29167330/endothelial-cell-metabolism
#13
REVIEW
Guy Eelen, Pauline de Zeeuw, Lucas Treps, Ulrike Harjes, Brian W Wong, Peter Carmeliet
Endothelial cells (ECs) are more than inert blood vessel lining material. Instead, they are active players in the formation of new blood vessels (angiogenesis) both in health and (life-threatening) diseases. Recently, a new concept arose by which EC metabolism drives angiogenesis in parallel to well-established angiogenic growth factors (e.g., vascular endothelial growth factor). 6-Phosphofructo-2-kinase/fructose-2,6-bisphosphatase-3-driven glycolysis generates energy to sustain competitive behavior of the ECs at the tip of a growing vessel sprout, whereas carnitine palmitoyltransferase 1a-controlled fatty acid oxidation regulates nucleotide synthesis and proliferation of ECs in the stalk of the sprout...
January 1, 2018: Physiological Reviews
https://www.readbyqxmd.com/read/29150442/functional-analyses-of-a-human-vascular-tumor-fos-variant-identify-a-novel-degradation-mechanism-and-a-link-to-tumorigenesis
#14
David G P van Ijzendoorn, Zary Forghany, Frauke Liebelt, Alfred C Vertegaal, Aart G Jochemsen, Judith V M G Bovée, Karoly Szuhai, David A Baker
Epithelioid hemangioma is a locally aggressive vascular neoplasm, found in bones and soft tissue, whose cause is currently unknown, but may involve oncogene activation. FOS was one of the earliest viral oncogenes to be characterized and normal cellular FOS forms part of the activator protein 1 (AP-1) transcription factor complex which plays a pivotal role in cell growth, differentiation and survival as well as the DNA damage response. Despite this, to date, a causal link between aberrant FOS function and naturally occurring tumors has not been established...
November 17, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29146905/pericytes-regulate-vegf-induced-endothelial-sprouting-through-vegfr1
#15
Hanna M Eilken, Rodrigo Diéguez-Hurtado, Inga Schmidt, Masanori Nakayama, Hyun-Woo Jeong, Hendrik Arf, Susanne Adams, Napoleone Ferrara, Ralf H Adams
Pericytes adhere to the abluminal surface of endothelial tubules and are required for the formation of stable vascular networks. Defective endothelial cell-pericyte interactions are frequently observed in diseases characterized by compromised vascular integrity such as diabetic retinopathy. Many functional properties of pericytes and their exact role in the regulation of angiogenic blood vessel growth remain elusive. Here we show that pericytes promote endothelial sprouting in the postnatal retinal vasculature...
November 17, 2017: Nature Communications
https://www.readbyqxmd.com/read/29141865/development-and-plasticity-of-meningeal-lymphatic-vessels
#16
Salli Antila, Sinem Karaman, Harri Nurmi, Mikko Airavaara, Merja H Voutilainen, Thomas Mathivet, Dmitri Chilov, Zhilin Li, Tapani Koppinen, Jun-Hee Park, Shentong Fang, Aleksanteri Aspelund, Mart Saarma, Anne Eichmann, Jean-Léon Thomas, Kari Alitalo
The recent discovery of meningeal lymphatic vessels (LVs) has raised interest in their possible involvement in neuropathological processes, yet little is known about their development or maintenance. We show here that meningeal LVs develop postnatally, appearing first around the foramina in the basal parts of the skull and spinal canal, sprouting along the blood vessels and cranial and spinal nerves to various parts of the meninges surrounding the central nervous system (CNS). VEGF-C, expressed mainly in vascular smooth muscle cells, and VEGFR3 in lymphatic endothelial cells were essential for their development, whereas VEGF-D deletion had no effect...
November 15, 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/29129724/retinal-vasculature-development-in-health-and-disease
#17
REVIEW
Senthil Selvam, Tejas Kumar, Marcus Fruttiger
Development of the retinal vasculature is based on highly coordinated signalling between different cell types of the retina, integrating internal metabolic requirements with external influences such as the supply of oxygen and nutrients. The developing mouse retinal vasculature is a useful model system to study these interactions because it is experimentally accessible for intra ocular injections and genetic manipulations, can be easily imaged and develops in a similar fashion to that of humans. Research using this model has provided insights about general principles of angiogenesis as well as pathologies that affect the developing retinal vasculature...
November 10, 2017: Progress in Retinal and Eye Research
https://www.readbyqxmd.com/read/29119674/assessment-of-hydrogels-for-bioprinting-of-endothelial-cells
#18
Leo Benning, Ludwig Gutzweiler, Kevin Tröndle, Julian Riba, Roland Zengerle, Peter Koltay, Stefan Zimmermann, G Björn Stark, Günter Finkenzeller
In tissue engineering applications, vascularization can be accomplished by co-implantation of tissue forming cells and endothelial cells (ECs), whereby the latter are able to form functional blood vessels. The use of three-dimensional (3D) bioprinting technologies has the potential to improve the classical tissue engineering approach because these will allow the generation of scaffolds with high spatial control of endothelial cell allocation. This study focuses on a side by side comparisons of popular commercially available bioprinting hydrogels (matrigel, fibrin, collagen, gelatin, agarose, Pluronic F-127, alginate and alginate/gelatin) in the context of their physicochemical parameters, their swelling/degradation characteristics, their biological effects on vasculogenesis-related EC parameters and their printability...
November 8, 2017: Journal of Biomedical Materials Research. Part A
https://www.readbyqxmd.com/read/29112161/collateral-damage-intended-cancer-associated-fibroblasts-and-vasculature-are-potential-targets-in-cancer-therapy
#19
REVIEW
Ana Cavaco, Maryam Rezaei, Stephan Niland, Johannes A Eble
After oncogenic transformation, tumor cells rewire their metabolism to obtain sufficient energy and biochemical building blocks for cell proliferation, even under hypoxic conditions. Glucose and glutamine become their major limiting nutritional demands. Instead of being autonomous, tumor cells change their immediate environment not only by their metabolites but also by mediators, such as juxtacrine cell contacts, chemokines and other cytokines. Thus, the tumor cells shape their microenvironment as well as induce resident cells, such as fibroblasts and endothelial cells (ECs), to support them...
November 7, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29093528/therapeutic-sirna-targeting-endothelial-kdr-decreases-portosystemic-collateralization-in-portal-hypertension
#20
Javier Gallego, Ester Garcia-Pras, Marc Mejias, Nuria Pell, Ute Schaeper, Mercedes Fernandez
Development of portosystemic collateral vessels and gastroesophageal varices is responsible for the most serious clinical consequences of portal hypertension, but effective clinical therapies are limited. Here we developed and investigated the therapeutic potential of an innovative liposomally-formulated short-interfering RNA (siRNA) technology based on clinical stage components, capable to attenuate production of the endothelial kinase insert domain receptor (KDR), which controls portosystemic collateralization and contributes to disease progression and aggravation...
November 1, 2017: Scientific Reports
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