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Prabhu Thirusangu, V Vigneshwaran, T Prashanth, B R Vijay Avin, Vikas H Malojirao, H Rakesh, Shaukath Ara Khanum, Riaz Mahmood, B T Prabhakar
Hypoxia is a feature of all solid tumours, contributing to tumour progression. Activation of HIF-1α plays a critical role in promoting tumour angiogenesis and metastasis. Since its expression is positively correlated with poor prognosis for cancer patients, HIF-1α is one of the most convincing anticancer targets. BP-1T is a novel antiproliferative agent with promising antiangiogenic effects. In the present study, the molecular mechanism underlying cytotoxic/antiangiogenic effects of BP-1T on tumour/non-tumour angiogenesis was evaluated...
October 14, 2016: Angiogenesis
Tessa D Nauta, Marloes van den Broek, Sue Gibbs, Tineke C T M van der Pouw-Kraan, Cees B Oudejans, Victor W M van Hinsbergh, Pieter Koolwijk
During prolonged hypoxic conditions, endothelial cells change their gene expression to adjust to the low oxygen environment. This process is mainly regulated by the hypoxia-inducible factors, HIF-1α and HIF-2α. Although endothelial cells do not form sprouts during prolonged hypoxic culturing, silencing of HIF-2α partially restores sprout formation. The present study identifies novel HIF-2α-target genes that may regulate endothelial sprouting during prolonged hypoxia. The gene expression profile of primary human microvascular endothelial cells (hMVECs) that were cultured at 20 % oxygen was compared to hMVECs that were cultured at 1 % oxygen for 14 days by using genome-wide RNA-sequencing...
October 3, 2016: Angiogenesis
Sónia Simão, Daniela F Santos, Gabriela A Silva
There is growing evidence on the role of ocular renin-angiotensin system (RAS) in the development of diabetic retinopathy (DR), particularly due to the trigger of oxidative stress and angiogenesis. Despite this there is no effective RAS-based therapy in DR capable of preventing retinal damage induced by RAS activation. We recently described that retinal pigment epithelium (RPE) cells express the main components of the RAS. We here propose to investigate the role of glucose upon the retinal RAS and whether aliskiren, a direct renin inhibitor, protects RPE cells from angiogenesis and oxidative stress...
October 1, 2016: Angiogenesis
Verónica Torres-Estay, Daniela V Carreño, Patricia Fuenzalida, Anica Watts, Ignacio F San Francisco, Viviana P Montecinos, Paula C Sotomayor, John Ebos, Gary J Smith, Alejandro S Godoy
BACKGROUND: Sex-related differences in the role of androgen have been reported in cardiovascular diseases and angiogenesis. Moreover, androgen receptor (AR) has been causally involved in the homeostasis of human prostate endothelial cells. However, levels of expression, functionality and biological role of AR in male- and female-derived human endothelial cells (ECs) remain poorly characterized. The objectives of this work were (1) to characterize the functional expression of AR in male- and female-derived human umbilical vein endothelial cell (HUVEC), and (2) to specifically analyze the biological effects of DHT, and the role of AR on these effects, in male-derived HUVECs (mHUVECs)...
September 27, 2016: Angiogenesis
Saskia von Stillfried, Jonas C Apitzsch, Josef Ehling, Tobias Penzkofer, Andreas H Mahnken, Ruth Knüchel, Jürgen Floege, Peter Boor
Renal microvascular rarefaction characterizes chronic kidney disease (CKD). In murine models of CKD, micro-CT imaging reflected capillary rarefaction using quantification of renal relative blood volume (rBV). In addition, micro-CT imaging revealed morphological alterations of the intrarenal vasculature including reduced vascular branching and lumen diameter. Here, we retrospectively quantified rBV in contrast-enhanced CT angiography in patients and found that, compared to non-CKD patients, those with CKD and renal fibrosis had significantly reduced rBV in the renal cortex...
October 2016: Angiogenesis
Alexandra M Ochsenbein, Sinem Karaman, Steven T Proulx, Rhea Goldmann, Jyothi Chittazhathu, Athanasia Dasargyri, Chloé Chong, Jean-Christophe Leroux, E Richard Stanley, Michael Detmar
Lymphatic vessels play important roles in fluid drainage and in immune responses, as well as in pathological processes including cancer progression and inflammation. While the molecular regulation of the earliest lymphatic vessel differentiation and development has been investigated in much detail, less is known about the control and timing of lymphatic vessel maturation in different organs, which often occurs postnatally. We investigated the time course of lymphatic vessel development on the pleural side of the diaphragmatic muscle in mice, the so-called submesothelial initial diaphragmatic lymphatic plexus...
October 2016: Angiogenesis
Rebecca E Conway, Camilo Rojas, Jesse Alt, Zora Nováková, Spencer M Richardson, Tori C Rodrick, Julio L Fuentes, Noah H Richardson, Jonathan Attalla, Samantha Stewart, Beshoy Fahmy, Cyril Barinka, Mallika Ghosh, Linda H Shapiro, Barbara S Slusher
Prostate-specific membrane antigen (PSMA) is a membrane-bound glutamate carboxypeptidase expressed in a number of tissues. PSMA participates in various biological functions depending on the substrate available in the particular tissue; in the brain, PSMA cleaves the abundant neuropeptide N-acetyl-aspartyl-glutamate to regulate release of key neurotransmitters, while intestinal PSMA cleaves polyglutamated peptides to supply dietary folate. PSMA expression is also progressively upregulated in prostate cancer where it correlates with tumor progression as well as in tumor vasculature, where it regulates angiogenesis...
October 2016: Angiogenesis
Jin-Hang Gao, Shi-Lei Wen, Shi Feng, Wen-Juan Yang, Yao-Yao Lu, Huan Tong, Rui Liu, Shi-Hang Tang, Zhi-Yin Huang, Ying-Mei Tang, Jin-Hui Yang, Hui-Qi Xie, Cheng-Wei Tang
Abnormal angiogenesis is critical for portal hypertension in cirrhosis. Except for etiological treatment, no efficient medication or regime has been explored to treat the early stage of cirrhosis when angiogenesis is initiated or overwhelming. In this study, we explored an anti-angiogenesis effort through non-cytotoxic drugs octreotide and celecoxib to treat early stage of cirrhotic portal hypertension in an animal model. Peritoneal injection of thioacetamide (TAA) was employed to induce liver cirrhosis in rats...
October 2016: Angiogenesis
Lisa M Ebert, Lih Y Tan, M Zahied Johan, Kay Khine Myo Min, Michaelia P Cockshell, Kate A Parham, Kelly L Betterman, Paceman Szeto, Samantha Boyle, Lokugan Silva, Angela Peng, YouFang Zhang, Andrew Ruszkiewicz, Andrew C W Zannettino, Stan Gronthos, Simon Koblar, Natasha L Harvey, Angel F Lopez, Mark Shackleton, Claudine S Bonder
Desmogleins (DSG) are a family of cadherin adhesion proteins that were first identified in desmosomes and provide cardiomyocytes and epithelial cells with the junctional stability to tolerate mechanical stress. However, one member of this family, DSG2, is emerging as a protein with additional biological functions on a broader range of cells. Here we reveal that DSG2 is expressed by non-desmosome-forming human endothelial progenitor cells as well as their mature counterparts [endothelial cells (ECs)] in human tissue from healthy individuals and cancer patients...
October 2016: Angiogenesis
Rui Zhang, Zhenying Han, Vincent Degos, Fanxia Shen, Eun-Jung Choi, Zhengda Sun, Shuai Kang, Michael Wong, Wan Zhu, Lei Zhan, Helen M Arthur, S Paul Oh, Marie E Faughnan, Hua Su
An abnormally high number of macrophages are present in human brain arteriovenous malformations (bAVM) with or without evidence of prior hemorrhage, causing unresolved inflammation that may enhance abnormal vascular remodeling and exacerbate the bAVM phenotype. The reasons for macrophage accumulation at the bAVM sites are not known. We tested the hypothesis that persistent infiltration and pro-inflammatory differentiation of monocytes in angiogenic tissues increase the macrophage burden in bAVM using two mouse models and human monocytes...
October 2016: Angiogenesis
Jelena Loegl, Erika Nussbaumer, Ursula Hiden, Alejandro Majali-Martinez, Nassim Ghaffari-Tabrizi-Wizy, Silvija Cvitic, Ingrid Lang, Gernot Desoye, Berthold Huppertz
The rapidly expanding feto-placental vasculature needs tight control by paracrine and endocrine mechanisms. Here, we focused on paracrine influence by trophoblast, the placental epithelium. We aimed to identify differences in regulation of feto-placental angiogenesis in early versus late pregnancy. To this end, the effect of conditioned media (CM) from early and late pregnancy human trophoblast was tested on network formation, migration and proliferation of human feto-placental endothelial cells. Only CM of late pregnancy trophoblast reduced network formation and migration...
July 2016: Angiogenesis
Katarzyna Korybalska, Ewelina Swora-Cwynar, Joanna Łuczak, Alina Kanikowska, Natasza Czepulis, Rafał Rutkowski, Andrzej Bręborowicz, Marian Grzymisławski, Janusz Witowski
OBJECTIVES: Substantial weight loss through intense dietary regimens is thought to ameliorate endothelial dysfunction in obesity. It is less clear whether similar improvements can be achieved with modest dietary interventions. This study aimed to identify the parameters of endothelial cell status in obesity that are affected by mild calorie restriction. METHODS: Human umbilical vein endothelial cells (EA.hy926 line) in culture were exposed pairwise to serum from 57 individuals with simple obesity (BMI > 30 kg/m(2)) collected before and after 8-week dietary intervention with energy deficit of 300-500 kcal/day...
July 2016: Angiogenesis
Mohamed Abo El-Asrar, Nancy Samir Elbarbary, Eman Abdel Rahman Ismail, AlShaimaa Abo Bakr
BACKGROUND: Angiopoietin-2 is a growth factor involved in the pathophysiology of vascular and inflammatory diseases such as arteriosclerosis. Carotid or aortic scans provide noninvasive screening tools for assessment of preclinical atherosclerosis in high-risk children. AIM: We assessed serum angiopoietin-2 in children and adolescents with type 1 diabetes mellitus as a potential marker for vascular complications in relation to glycemic control, inflammation and vascular structure...
July 2016: Angiogenesis
Douglas A MacDonald, Joel Martin, Kathir K Muthusamy, Jiann-Kae Luo, Erica Pyles, Ashique Rafique, Tammy Huang, Terra Potocky, Yang Liu, Jingtai Cao, Françoise Bono, Nathalie Delesque, Pierre Savi, John Francis, Ali Amirkhosravi, Todd Meyer, Carmelo Romano, Meredith Glinka, George D Yancopoulos, Neil Stahl, Stanley J Wiegand, Nicholas Papadopoulos
Anti-vascular endothelial growth factor (VEGF) therapies have improved clinical outcomes for patients with cancers and retinal vascular diseases. Three anti-VEGF agents, pegaptanib, ranibizumab, and aflibercept, are approved for ophthalmic indications, while bevacizumab is approved to treat colorectal, lung, and renal cancers, but is also used off-label to treat ocular vascular diseases. The efficacy of bevacizumab relative to ranibizumab in treating neovascular age-related macular degeneration has been assessed in several trials...
July 2016: Angiogenesis
Du Yang, Chunna Jin, Hong Ma, Mingyuan Huang, Guo-Ping Shi, Jianan Wang, Meixiang Xiang
Ischemic cardiovascular disease remains one of the leading causes of morbidity and mortality in the world. Proangiogenic therapy appears to be a promising and feasible strategy for the patients with ischemic cardiovascular disease, but the results of preclinical and clinical trials are limited due to the complicated mechanisms of angiogenesis. Facilitating the formation of functional vessels is important in rescuing the ischemic cardiomyocytes. EphrinB2/EphB4, a novel pathway in angiogenesis, plays a critical role in both microvascular growth and neovascular maturation...
July 2016: Angiogenesis
Kai Lu, Madhavi Bhat, Sujit Basu
Angiogenesis, or new blood vessel formation, is an important process in the pathogenesis of several diseases and thus has been targeted for the prevention and treatment for many disorders. However, the anti-angiogenic agents that are currently in use are mainly synthetic compounds and humanized monoclonal antibodies, which are either expensive or toxic, thereby limiting their use in many patients. Therefore, it is necessary to identify less toxic, inexpensive, novel and effective anti-angiogenic molecules. Several studies have indicated that natural plant products can meet these criteria...
July 2016: Angiogenesis
Saima Subhani, Divya Teja Vavilala, Mridul Mukherji
Aberrant activation of the hypoxia inducible factor (HIF) pathway causing overexpression of angiogenic genes, like vascular endothelial growth factor (VEGF), is one of the underlying causes of ocular neovascularization (NV) and metastatic cancer. Consistently, along with surgical interventions, a number of anti-VEGF agents have been approved by FDA for the treatment of ocular neovascular diseases. These anti-VEGF agents, like ranibizumab/lucentis, have revolutionized the treatment in the past decade. However, substantial vision improvement is observed only in a subset of age-related macular degeneration patients receiving ranibizumab...
July 2016: Angiogenesis
Michael P Craig, Saulius Sumanas
At least thirteen ETS-domain transcription factors are expressed during embryonic hematopoietic or vascular development and potentially function in the formation and maintenance of the embryonic vasculature or blood lineages. This review summarizes our current understanding of the specific roles played by ETS factors in vasculogenesis and angiogenesis and the implications of functional redundancies between them.
July 2016: Angiogenesis
Mary E Ziegler, Michaela M S Hatch, Nan Wu, Steven A Muawad, Christopher C W Hughes
The chemokine CXCL12, through its receptor CXCR4, positively regulates angiogenesis by promoting endothelial cell (EC) migration and tube formation. However, the relevant downstream signaling pathways in EC have not been defined. Similarly, the upstream activators of mTORC2 signaling in EC are also poorly defined. Here, we demonstrate for the first time that CXCL12 regulation of angiogenesis requires mTORC2 but not mTORC1. We find that CXCR4 signaling activates mTORC2 as indicated by phosphorylation of serine 473 on Akt and does so through a G-protein- and PI3K-dependent pathway...
July 2016: Angiogenesis
Dimitar Tasev, Lara S F Konijnenberg, Joana Amado-Azevedo, Michiel H van Wijhe, Pieter Koolwijk, Victor W M van Hinsbergh
Endothelial colony-forming cells (ECFC) are grown from circulating CD34(+) progenitors present in adult peripheral blood, but during in vitro expansion part of the cells lose CD34. To evaluate whether the regulation of CD34 characterizes the angiogenic phenotypical features of PB-ECFCs, we investigated the properties of CD34(+) and CD34(-) ECFCs with respect to their ability to form capillary-like tubes in 3D fibrin matrices, tip-cell gene expression, and barrier integrity. Selection of CD34(+) and CD34(-) ECFCs from subcultured ECFCs was accomplished by magnetic sorting (FACS: CD34(+): 95 % pos; CD34(-): 99 % neg)...
July 2016: Angiogenesis
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