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Vessel sprouting

Loiy E Ahmed Hassan, Saad S Dahham, Sultan Ayesh Mohammed Saghir, Abdelhafeez M A Mohammed, Nagla M Eltayeb, Amin Malik Shah Abdul Majid, Aman Shah Abdul Majid
BACKGROUND: Balanite aegyptiaca (L.) Delile, is a plant with extensive medicinal properties. Its stem bark is traditionally known for its spasmolytic and antiepileptic properties and used to treat yellow fever, jaundice and syphilis. Angiogenesis (sprouting of new blood vessels) is crucial for tumor growth and metastasis. The goal of this study is investigate the antiangiogenic, cytotoxicity and antioxidant activity as well as antitumor in vivo properties of B. aegyptiaca stem bark extracts...
October 19, 2016: BMC Complementary and Alternative Medicine
Jingjiang Pi, Ting Tao, Tao Zhuang, Huimin Sun, Xiaoli Chen, Jie Liu, Yu Cheng, Zuoren Yu, Helen H Zhu, Wei-Qiang Gao, Yuanzhen Suo, Xunbin Wei, Paul Chan, Xiangjian Zheng, Ying Tian, Edward Morrisey, Lin Zhang, Yuzhen Zhang
RATIONALE: Angiogenic hypersprouting and leaky vessels are essential for tumor growth. MicroRNAs have unique therapeutic advantages by targeting multiple pathways of tumor-associated angiogenesis, but the function of individual miRNAs of miR302-367cluster in angiogenesis and tumors has not yet been fully evaluated. OBJECTIVE: To investigate the functions of miR302-367 in developmental angiogenesis and tumor angiogenesis and explore the molecular mechanisms of microRNA for the treatment of pathological neovascularization-related diseases...
October 18, 2016: Circulation Research
Karen Beets, Michael W Staring, Nathan Criem, Elke Maas, Niels Schellinx, Susana M Chuva de Sousa Lopes, Lieve Umans, An Zwijsen
BACKGROUND: Bone morphogenetic protein (BMP) signalling has emerged as a fundamental pathway in endothelial cell biology and deregulation of this pathway is implicated in several vascular disorders. BMP signalling output in endothelial cells is highly context- and dose-dependent. Phosphorylation of the BMP intracellular effectors, SMAD1/5/9, is routinely used to monitor BMP signalling activity. To better understand the in vivo context-dependency of BMP-SMAD signalling, we investigated differences in BMP-SMAD transcriptional activity in different vascular beds during mouse embryonic and postnatal stages...
October 10, 2016: BMC Developmental Biology
Elisabeth Naschberger, Andrea Liebl, Vera S Schellerer, Manuela Schütz, Nathalie Britzen-Laurent, Patrick Kölbel, Ute Schaal, Lisa Haep, Daniela Regensburger, Thomas Wittmann, Ludger Klein-Hitpass, Tilman T Rau, Barbara Dietel, Valérie S Méniel, Alan R Clarke, Susanne Merkel, Roland S Croner, Werner Hohenberger, Michael Stürzl
Different tumor microenvironments (TMEs) induce stromal cell plasticity that affects tumorigenesis. The impact of TME-dependent heterogeneity of tumor endothelial cells (TECs) on tumorigenesis is unclear. Here, we isolated pure TECs from human colorectal carcinomas (CRCs) that exhibited TMEs with either improved (Th1-TME CRCs) or worse clinical prognosis (control-TME CRCs). Transcriptome analyses identified markedly different gene clusters that reflected the tumorigenic and angiogenic activities of the respective TMEs...
October 10, 2016: Journal of Clinical Investigation
Valeria Perugini, Anna L Guildford, Joana Silva-Correia, Joaquim M Oliveira, Steven T Meikle, Rui L Reis, Matteo Santin
Damage of non-vascularised tissues such as cartilage and cornea can result in healing processes accompanied by a non-physiological angiogenesis. Peptidic aptamers have recently been reported to block the vascular endothelial growth factor (VEGF). However, the therapeutic applications of these aptamers is limited due to their short half-life in vivo. In this work, an enhanced stability and bioavailability of a known VEGF blocker aptamer sequence (WHLPFKC) was pursued through its tethering of molecular scaffolds based on hyperbranched peptides, the poly(ɛ-lysine) dendrons, bearing three branching generations...
October 8, 2016: Journal of Tissue Engineering and Regenerative Medicine
David W Howell, Camille L Duran, Shang-Pu Tsai, Sarah E Bondos, Kayla J Bayless
Successful design of tissue engineering scaffolds must include the ability to stimulate vascular development by incorporating angiogenic growth factors. Current approaches can allow diffusion of growth factors, incorporate active factors randomly, or can leave residual toxins. We addressed these problems by genetically fusing the gene encoding Vascular Endothelial Growth Factor (VEGF) with the Ultrabithorax (Ubx) gene to produce fusion proteins capable of self-assembly into materials. We demonstrate that VEGF-Ubx materials enhance human endothelial cell migration, prolong cell survival, and dose-dependently activate the VEGF signaling pathway...
October 7, 2016: Biomacromolecules
Pirjo Spuul, Thomas Daubon, Bettina Pitter, Florian Alonso, Isabelle Fremaux, IJsbrand Kramer, Eloi Montanez, Elisabeth Génot
During angiogenic sprouting, endothelial tip cells emerge from existing vessels in a process that requires vascular basement membrane degradation. Here, we show that F-actin/cortactin/P-Src-based matrix-degrading microdomains called podosomes contribute to this step. In vitro, VEGF-A/Notch signaling regulates the formation of functional podosomes in endothelial cells. Using a retinal neovascularization model, we demonstrate that tip cells assemble podosomes during physiological angiogenesis in vivo. In the retina, podosomes are also part of an interconnected network that surrounds large microvessels and impinges on the underlying basement membrane...
October 4, 2016: Cell Reports
Pavel I Nedvetsky, Xiaocheng Zhao, Thomas Mathivet, Irene M Aspalter, Fabio Stanchi, Ross J Metzger, Keith E Mostov, Holger Gerhardt
cAMP-dependent protein kinase A (PKA) is a ubiquitously expressed serine/threonine kinase that regulates a variety of cellular functions. Here, we demonstrate that endothelial PKA activity is essential for vascular development, specifically regulating the transition from sprouting to stabilization of nascent vessels. Inhibition of endothelial PKA by endothelial cell-specific expression of dominant-negative PKA in mice led to perturbed vascular development, hemorrhage and embryonic lethality at mid-gestation...
October 1, 2016: Development
Ayumi Nagasawa-Masuda, Kenta Terai
Vasculogenesis is essential during early development to construct networks transporting oxygen, blood and nutrients. Tip and stalk cells are specialized endothelial cells involved in novel vessel formation because of their behavior such as sprouting as a leading cell and following tip cell. However, the spatiotemporal details determining the emergence of these cells are unknown. Here, we first show that the ERK activity in endothelial cells represents the precursor of tip and stalk cells for vasculogenesis in zebrafish...
October 3, 2016: Genes to Cells: Devoted to Molecular & Cellular Mechanisms
Delia Ricolo, Myrto Deligiannaki, Jordi Casanova, Sofia J Araújo
Centrosome amplification is a hallmark of cancer, although we are still far from understanding how this process affects tumorigenesis [1, 2]. Besides the contribution of supernumerary centrosomes to mitotic defects, their biological effects in the post-mitotic cell are not well known. Here, we exploit the effects of centrosome amplification in post-mitotic cells during single-cell branching. We show that Drosophila tracheal cells with extra centrosomes branch more than wild-type cells. We found that mutations in Rca1 and CycA affect subcellular branching, causing tracheal tip cells to form more than one subcellular lumen...
September 17, 2016: Current Biology: CB
Pardhasaradhi Mathi, Ganesh Kumar Veeramachaneni, K Kranthi Raj, Venkateswara Rao Talluri, Venkata Raman Bokka, Mahendran Botlagunta
Sophora interrupta Bedd, (Fabaceae) is used in Indian folk medicine to treat cancer. Angiogenesis is one of the crucial characteristics of cancer metastasis and is regulated by vascular endothelial growth factor (VEGF). In this study, we examined the antiangiogenic properties of the root ethyl acetate extract of Sophora interrupta by various methods. In vitro antioxidant activity (100-600 μg/ml) of S. interrupta ethyl acetate (SEA) extract was evaluated by DPPH and ABTS, anti-inflammatory activity (50, 100 and 150 μg/ml) by estimating nitric oxide (NO) levels, anti-angiogenic activity (200 and 500 μg/ml) was validated by chorio allantoic membrane (CAM) assay and in silico molecular dynamic (MD) simulations analyses (25 ns) were performed to identify the anti-angiogenic compounds extracted from root extract...
October 2016: Journal of Molecular Modeling
Lindsey Dew, William R English, Chuh K Chong, Sheila MacNeil
One of the main challenges currently faced by tissue engineers is the loss of tissues post implantation due to delayed neovascularization. Several strategies are under investigation to create vascularized tissue but none have yet overcome this problem. In this study we produced a decellularized natural vascular scaffold from rat intestine to use as an in vitro platform for neovascularization studies for tissue engineered constructs. Decellularization resulted in almost complete (97%) removal of nuclei and DNA, while collagen, glycosaminoglycans and laminin content was preserved...
September 27, 2016: Tissue Engineering. Part A
Despina Bazou, Mei Rosa Ng, Jonathan W Song, Shan Min Chin, Nir Maimon, Lance L Munn
Angiogenesis requires the coordinated growth and migration of endothelial cells (ECs), with each EC residing in the vessel wall integrating local signals to determine whether to remain quiescent or undergo morphogenesis. These signals include vascular endothelial growth factor (VEGF) and flow-induced mechanical stimuli such as interstitial flow, which are both elevated in the tumor microenvironment. However, it is not clear how VEGF signaling and mechanobiological activation due to interstitial flow cooperate during angiogenesis...
September 27, 2016: Scientific Reports
Changyue Xue, Jiamin Xie, Dan Zhao, Shiyu Lin, Tengfei Zhou, Sirong Shi, Xiaoru Shao, Yunfeng Lin, Bofeng Zhu, Xiaoxiao Cai
OBJECTIVES: The aim of the study was to investigate the role of the JAK/STAT3 signalling pathway in angiogenesis. MATERIALS AND METHODS: The model established in vitro, involved a 3D collagen gel being implanted with endothelial cells (ECs) from red fluorescent protein-labelled mice, and adipose-derived stromal cells (ASCs) from green fluorescent protein-labelled mice. Phenomena of angiogenesis, after treatment by the inhibitor and the activator of JAK/STAT3 pathway respectively, were observed using confocal laser scanning microscopy...
September 25, 2016: Cell Proliferation
Diana Vicente, Blanca Hernández, Vanessa Segura, Desirée Pascual, Giacomo Fornaciari, Fermí Monto, Vicente Mirabet, M Carmen Montesinos, Pilar DʼOcon
The sprouting of new vessels is greatly influenced by the procedure chosen. We sought to optimize the experimental conditions of the angiogenic growth of fresh and cryopreserved vessels cultured in Matrigel with the aim to use this system to analyze the pharmacological modulation of the process. Segments of second-order branches of rat mesenteric resistance arteries, thoracic aorta of rat or mouse, and cryopreserved rat aorta and human femoral arteries were cultured in Matrigel for 7-21 days in different mediums, as well as in the absence of endothelial or adventitia layer...
September 2016: Journal of Cardiovascular Pharmacology
Alfred Gugerell, Johanna Kober, Melanie Schmid, Elisabeth Buchberger, Lars-Peter Kamolz, Maike Keck
BACKGROUND: Botulinum (neuro)toxin A (BoNT) is widely used in the field of plastic and reconstructive surgery. Among treatment of pain, hyperhidrosis, or aesthetic purposes, it is also used to enhance wound healing and prevent excessive scar formation. Some clinical data already exist, but only little is known on a cellular level. The aim of this study was to evaluate the effect of BoNT on cells essential for wound healing in vitro. Therefore, primary human keratinocytes and endothelial cells were treated with different concentrations of BoNT and tested on proliferation, migration, and angiogenic behavior...
August 2016: Plastic and Reconstructive Surgery. Global Open
Masahiro Shin, Ira Male, Timothy J Beane, Jacques A Villefranc, Fatma O Kok, Lihua J Zhu, Nathan D Lawson
Vascular endothelial growth factor C (Vegfc) activates its receptor, Flt4, to induce lymphatic development. However, the signals that act downstream of Flt4 in this context in vivo remain unclear. To better understand Flt4 signaling, we generated zebrafish bearing a deletion in the Flt4 cytoplasmic domain that eliminates tyrosines Y1226 and 1227. Embryos bearing this deletion failed to initiate sprouting or differentiation of trunk lymphatic vessels and did not form a thoracic duct. Deletion of Y1226/7 prevented ERK phosphorylation in lymphatic progenitors while ERK inhibition blocked trunk lymphatic sprouting and differentiation...
September 12, 2016: Development
Jung Min Ha, Seo Yeon Jin, Hye Sun Lee, Hwa Kyoung Shin, Dong Hyung Lee, Sang Heon Song, Chi Dae Kim, Sun Sik Bae
Angiogenesis plays an essential role in embryo development, tissue repair, inflammatory diseases, and tumor growth. In the present study, we showed that endothelial nitric oxide synthase (eNOS) regulates retinal angiogenesis. Mice that lack eNOS showed growth retardation, and retinal vessel development was significantly delayed. In addition, the number of tip cells and filopodia length were significantly reduced in mice lacking eNOS. Retinal endothelial cell proliferation was significantly blocked in mice lacking eNOS, and EMG-2-induced endothelial cell sprouting was significantly reduced in aortic vessels isolated from eNOS-deficient mice...
September 2016: Korean Journal of Physiology & Pharmacology
ZhiQiang Chen, Lu Zhang, JingTing Yu, LiangKe Chen, Bo Zhou
The potential to promote neovascularization in ischemic tissues using exogenous agents is an attractive avenue for therapeutics. To identify novel pro-angiogenic small-molecule compound, we screened a series of resveratrol methylated derivatives and identified 3,3',4,4', 5,5'-hexamethoxy-trans-stilbene (3,3',4,4',5,5'-HMS) potently promotes proliferation, migration, invasion and tube formation of human umbilical vein VECs (HUVECs) in vitro. Furthermore, 3,3',4,4',5,5'-HMS accelerates neo-vessels sprouting of rat aortic rings ex vivo, and neovascularization of chick chorioallantoic membrane (CAM) and mouse matrigel plugs in vivo...
August 31, 2016: European Journal of Pharmacology
M Shin, T Beane, A Quillien, I Male, L J Zhu, N D Lawson
Vascular endothelial growth factor a (Vegfa) is essential for blood vessel formation and can induce activation of numerous signaling effectors in endothelial cells. However, it is unclear how and where these function in developmental contexts during vascular morphogenesis. To address this issue, we have visualized activation of presumptive Vegfa effectors at single cell resolution in zebrafish blood vessels. From these studies, we find that phosphorylation of the serine/threonine kinase ERK (pERK) preferentially occurs in endothelial cells undergoing angiogenesis, but not in committed arterial endothelial cells...
August 30, 2016: Development
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