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Hongyou Yu, Corey S Moran, Alexandra F Trollope, Lynn Woodward, Robert Kinobe, Catherine M Rush, Jonathan Golledge
Angiogenesis and inflammation are implicated in aortic aneurysm and atherosclerosis and regulated by angiopoietin-2 (Angpt2). The effect of Angpt2 administration on experimental aortic aneurysm and atherosclerosis was examined. Six-month-old male apolipoprotein E deficient (ApoE(-/-)) mice were infused with angiotensin II (AngII) and administered subcutaneous human Fc-protein (control) or recombinant Angpt2 (rAngpt2) over 14 days. Administration of rAngpt2 significantly inhibited AngII-induced aortic dilatation and rupture of the suprarenal aorta (SRA), and development of atherosclerosis within the aortic arch...
October 21, 2016: Scientific Reports
Hosana G Rodrigues, Marco A R Vinolo, Fabio T Sato, Juliana Magdalon, Carolina M C Kuhl, Ana S Yamagata, Ana Flávia M Pessoa, Gabriella Malheiros, Marinilce F Dos Santos, Camila Lima, Sandra H Farsky, Niels O S Camara, Maria R Williner, Claudio A Bernal, Philip C Calder, Rui Curi
INTRODUCTION: Impaired wound healing has been widely reported in diabetes. Linoleic acid (LA) accelerates the skin wound healing process in non-diabetic rats. However, LA has not been tested in diabetic animals. OBJECTIVES: We investigated whether oral administration of pure LA improves wound healing in streptozotocin-induced diabetic rats. METHODS: Dorsal wounds were induced in streptozotocin-induced type-1 diabetic rats treated or not with LA (0...
2016: PloS One
Ke-Wei Tian, Fan Zhang, Hong Jiang, Beibei Wang, Shu Han
Multiple sclerosis (MS) is a chronic neurological disorder that affects the central nervous system (CNS), and results in CNS inflammation and damage to myelin. In this study, we examined the possible synergistic effects of C16, angiopoietin-1 (Ang-1) and regeneration gene protein 2 (Reg-2) in alleviating inflammation in an acute experimental autoimmune encephalomyelitis (EAE) model. We employed multiple histological, morphological and iconographic assays to examine the effect of those drugs on disease onset, clinical scores and behavioral deficits...
October 19, 2016: Journal of Anatomy
Abdul Jalil Rufaihah, Nurul Azizah Johari, Srirangam Ramanujam Vaibavi, Marian Plotkin, Do Thi Di Thien, Theodoros Kofidis, Dror Seliktar
Acute myocardial infarction (MI) caused by ischemia is the most common cause of cardiac dysfunction. While growth factor therapy is promising, the retention in the highly vascularized myocardium is limited and prevents sustained activation needed for adequate cellular responses. Here, we demonstrated the use of polyethylene glycol-fibrinogen (PF) hydrogels for sustained dual delivery of vascular endothelial growth factor (VEGF) and angiopoietin-1 (ANG-1) to enhance myocardial repair and function. VEGF and ANG-1 were incorporated in PF hydrogels and their in vitro characteristics were studied...
October 15, 2016: Acta Biomaterialia
Alexander Reinthaller
Angiogenesis plays a pivotal role in normal ovarian physiology as well as in the formation and progression of ovarian cancer. Several well-designed phase II and III trials studied the efficacy of antiangiogenic agents in advanced ovarian cancer. The results of these trials demonstrated significantly prolonged progression-free survival when antiangiogenic agents were used as a maintenance therapy. To date, no effect on overall survival could be ascertained. The most widely studied antiangiogenic agent, bevacizumab - a monoclonal humanized antibody against vascular endothelial growth factor - was effective in all phases of the disease (first-line therapy, platinum-sensitive and platinum-resistant recurrence)...
2016: Memo
Alexandra Jochmans-Lemoine, Manju Shahare, Jorge Soliz, Vincent Joseph
We previously reported that rats and mice that have been raised for more than 30 generations in La Paz, Bolivia (3600m), display divergent physiological responses to high altitude (HA), including improved respiratory and metabolic control in mice. In the present study we asked whether these traits would also be present in response to hypoxia at sea level (SL). To answer this question, we exposed rats (SD) and mice (FVB) to normoxia (21% O2) or hypoxia (15 and 12% O2) for 6 hours and measured ventilation and metabolic rate (whole body plethysmography), and expression of the transcription factor HIF-1α (ELISA and Mass Spectrometry) and other proteins whose expression are regulated by hypoxia (Glucose Transporter 1, Pyruvate Dehydrogenase Kinase 1, and Angiopoietin 2 - Mass Spectrometry) in the brainstem...
October 14, 2016: Journal of Experimental Biology
Jörg T Regula, Peter Lundh von Leithner, Richard Foxton, Veluchamy A Barathi, Chui Ming Gemmy Cheung, Sai Bo Bo Tun, Yeo Sia Wey, Daiju Iwata, Miroslav Dostalek, Jörg Moelleken, Kay G Stubenrauch, Everson Nogoceke, Gabriella Widmer, Pamela Strassburger, Michael J Koss, Christian Klein, David T Shima, Guido Hartmann
Anti-angiogenic therapies using biological molecules that neutralize vascular endothelial growth factor-A (VEGF-A) have revolutionized treatment of retinal vascular diseases including age-related macular degeneration (AMD). This study reports preclinical assessment of a strategy to enhance anti-VEGF-A monotherapy efficacy by targeting both VEGF-A and angiopoietin-2 (ANG-2), a factor strongly upregulated in vitreous fluids of patients with retinal vascular disease and exerting some of its activities in concert with VEGF-A...
October 14, 2016: EMBO Molecular Medicine
Nathalie Thorin-Trescases, Doug Hayami, Carol Yu, Xiaoyan Luo, Albert Nguyen, Jean-François Larouche, Julie Lalongé, Christine Henri, André Arsenault, Mathieu Gayda, Martin Juneau, Jean Lambert, Eric Thorin, Anil Nigam
Pro-inflammatory angiopoietin-like 2 (angptl2) promotes endothelial dysfunction in mice and circulating angptl2 is higher in patients with cardiovascular diseases. We previously reported that a single bout of physical exercise was able to reduce angptl2 levels in coronary patients. We hypothesized that chronic exercise would reduce angptl2 in patients with post-acute coronary syndrome (ACS) and endothelial dysfunction. Post-ACS patients (n = 40, 10 women) were enrolled in a 3-month exercise-based prevention program...
2016: PloS One
Mohamed Abu-Farha, Irina Al-Khairi, Preethi Cherian, Betty Chandy, Devarajan Sriraman, Asma Alhubail, Faisal Al-Refaei, Abdulmohsen AlTerki, Jehad Abubaker
BACKGROUND: Hypertriglyceridemia is associated with increased risk for cardiovascular diseases and type 2 diabetes (T2D). Angiopoietin like proteins particularly 3, 4 and recently 8 are well established regulators of plasma triglyceride level through regulating the activity of lipoprotein lipase. Plasma level and association between ANGPTL3, 4 and 8 is not well established in human subjects. This study was designed to establish the level of these proteins in plasma and adipose tissues and investigate the association between ANGPTL8 with ANGPTL3 and 4 in T2D and non-diabetics subjects...
October 13, 2016: Lipids in Health and Disease
Jeremy Ben-Shoshan, Arie Steinvil, Yaron Arbel, Yan Topilsky, Leehee Barak, Michal Entin-Meer, Ran Levy, Arie Lorin Schwartz, Gad Keren, Ariel Finkelstein, Shmuel Banai
BACKGROUND: Transcatheter aortic valve replacement (TAVR) exposes the systemic vasculature to increased mechanical forces. Endothelial adaptation to mechanical stimuli is associated with angiogenic activation through various growth factors. We studied the potential angiogenic shift evoked by TAVR. METHODS: From a cohort of 69 consecutive patients undergoing TAVR, we excluded patients with conditions known to affect angiogenic factors, and serum vascular endothelial growth factor (VEGF) and angiopoietin (Ang)-1 and Ang-2 were assessed by ELISA...
June 25, 2016: Canadian Journal of Cardiology
Zuzanna Drebert, Mark MacAskill, Dahlia Doughty-Shenton, Karolien De Bosscher, Marc Bracke, Patrick W F Hadoke, Ilse M Beck
Angiogenesis is important in cancer progression and can be influenced by tumor-associated myofibroblasts. We addressed the hypothesis that glucocorticoids indirectly affect angiogenesis by altering the release of pro-angiogenic factors from colon cancer-derived myofibroblasts. Our study shows that glucocorticoids reduced prostanoids, urokinase-type plasminogen activator (uPA) and angiopoietin-like protein-2 (ANGPTL2) levels, but increased angiogenin (ANG) in supernatant from human CT5.3hTERT colon cancer-derived myofibroblasts...
October 4, 2016: Vascular Pharmacology
Tobias Hilbert, Kathrin Dornbusch, Georg Baumgarten, Andreas Hoeft, Stilla Frede, Sven Klaschik
Increased pulmonary vascular resistance is a critical complication in sepsis. Toll-like receptor (TLR) as well as angiopoietin (ANG) signaling both contribute to the emergence of pulmonary arterial hypertension. We hypothesized that TLR stimulation by bacterial ligands directly affects expression and secretion of ligands and receptors of the angiopoietin/TIE axis. Microvascular endothelial (HPMEC) and smooth muscle cells (SMC) of pulmonary origin were incubated with thrombin and with ligands for TLR2, -4, -5, and -9...
October 6, 2016: Clinical and Experimental Pharmacology & Physiology
Andrea L Conroy, Michael Hawkes, Chloe R McDonald, Hani Kim, Sarah J Higgins, Kevin R Barker, Sophie Namasopo, Robert O Opoka, Chandy C John, W Conrad Liles, Kevin C Kain
Background.  Host responses to infection are critical determinants of disease severity and clinical outcome. The development of tools to risk stratify children with malaria is needed to identify children most likely to benefit from targeted interventions. Methods.  This study investigated the kinetics of candidate biomarkers of mortality associated with endothelial activation and dysfunction (angiopoietin-2 [Ang-2], soluble FMS-like tyrosine kinase-1 [sFlt-1], and soluble intercellular adhesion molecule-1 [sICAM-1]) and inflammation (10 kDa interferon γ-induced protein [CXCL10/IP-10] and soluble triggering receptor expressed on myeloid cells-1 [sTREM-1]) in the context of a randomized, double-blind, placebo-controlled, parallel-arm trial evaluating inhaled nitric oxide versus placebo as adjunctive therapy to parenteral artesunate for severe malaria...
September 2016: Open Forum Infectious Diseases
Nan-Nan Sun, Chong Li, Lei Zhou, Yan Peng, Bin Zhang, Xian-Ming Qiu, Zhi-Ming Jiang, Jiang Xu
OBJECTIVE: To investigate the role of angiopoietin-2 (Ang-2) in tumor necrosis factor-α (TNF-α) induced apoptosis of alveolar epithelium cells (AECs). METHODS: TNF-α was used to induce human alveolar epithelial HPAEpiC cells, and Ang-2 siRNA vector was transfected to the HPAEpiC cells. RT-PCR and Western blot were used. TUNEL staining was applied to observe apoptosis, and annexin V-FITC-PI staining was used to calculate apoptosis rate. RESULTS: mRNA and protein expressions of Ang-2, activated Bax, and cleaved caspase-3 in HPAEpiC cells were up-regulated, but the expression level of Bcl-2 decreased (P < 0...
July 27, 2016: Biochemistry and Cell Biology, Biochimie et Biologie Cellulaire
Eun-Joo Jeon, Munkhtugs Davaatseren, Jin-Taek Hwang, Jae Ho Park, Haeng Jeon Hur, Ae Sin Lee, Mi Jeong Sung
In patients with inflammatory bowel disease (IBD), inflammation is induced and maintained by lymphangiogenesis and angiogenesis. 3,3'-Diindolylmethane (DIM) is a natural product formed in acidic conditions from indole-3-carbinol in cruciferous vegetables, and it is known for its chemotherapeutic activity. This study evaluated DIM's effects on angiogenesis, lymphangiogenesis, and inflammation in a mouse colitis model. Experimental colitis was induced in mice by administering 3% dextran sulfate sodium (DSS) via drinking water...
October 4, 2016: Journal of Agricultural and Food Chemistry
Yuanyuan Liu, Jing Gao, Shuangsheng Huang, Lamei Hu, Zhiqiang Wang, Zheyuan Wang, Xiao Chen, Xiaoyu Zhang, Wenguang Li
Reactive oxygen species (ROS) are involved in the signaling pathway and are triggered by angiogenic factors, including vascular endothelial growth factor and angiopoietins. 4-isothiocyanate-2, 2, 6, 6-tetramethyl piperidinooxyl (4-ISO-Tempo) is one of the nitroxides that exhibits antioxidant activity. However, the anti-angiogenic effect of 4-ISO-Tempo remains unknown. The aim of this study was to investigate the effect of 4-ISO-Tempo on tumor proliferation and angiogenesis as well as its underlying mechanisms...
October 2016: Oncology Letters
Annamarie C Dalton, Tomer Shlamkovitch, Niv Papo, William A Barton
Functional cross-talk between Tie2 and Integrin signaling pathways is essential to coordinate endothelial cell adhesion and migration in response to the extracellular matrix, yet the mechanisms behind this phenomenon are unclear. Here, we examine the possibility that receptor cross-talk is driven through uncharacterized Tie-integrin interactions on the endothelial surface. Using a live cell FRET-based proximity assay, we monitor Tie-integrin receptor recognition and demonstrate that both Tie1 and Tie2 readily associate with integrins α5ß1 and αVß3 through their respective ectodomains...
2016: PloS One
Renzhi Wang, Yakun Yang, Miaomiao Sheng, Dechao Bu, Fengming Huang, Xiaohai Liu, Cuiqi Zhou, Congxin Dai, Bowen Sun, Jindong Zhu, Yi Qiao, Yong Yao, Huijuan Zhu, Lin Lu, Hui Pan, Ming Feng, Kan Deng, Bing Xing, Wei Lian, Yi Zhao, Chengyu Jiang
Adrenocorticotrophin (ACTH)-secreting pituitary adenoma, also known as Cushing disease (CD), is rare and causes metabolic syndrome, cardiovascular disease and osteoporosis due to hypercortisolism. However, the molecular pathogenesis of CD is still unclear because of a lack of human cell lines and animal models. Here, we study 106 clinical characteristics and gene expression changes from 118 patients, the largest cohort of CD in a single-center. RNA deep sequencing is used to examine genotypic changes in nine paired female ACTH-secreting pituitary adenomas and adjacent nontumorous pituitary tissues (ANPT)...
September 29, 2016: International Journal of Molecular Sciences
Yu-Ping Zhang, Chang Liu, Lei Ye, Na Yu, Yuan-Ning Ye, Wen-Rong Sun, Lin Wu, Fang-Yu Wang
BACKGROUND: Biomarkers for the early prediction of the severity of acute pancreatitis (AP) are urgently needed for clinical management of the disease. Angiopoietin-2 (Ang-2), one of the autocrine peptides that reduce endothelial permeability, has been found to be associated with various diseases, including inflammatory disorders. AIMS: This study aimed to determine whether serum Ang-2 could serve as a noninvasive biomarker for the early prediction of persistent organ failure (POF) in acute pancreatitis...
September 29, 2016: Digestive Diseases and Sciences
Jaemin Lee, Jinhoi Song, Eun-Soo Kwon, Seongyea Jo, Min Kyung Kang, Yeon Jeong Kim, Yeonsil Hwang, Hosung Bae, Tae Heung Kang, Suhwan Chang, Hee Jun Cho, Song Cheol Kim, Seokho Kim, Sang Seok Koh
CTHRC1 (collagen triple-helix repeat-containing 1), a protein secreted during the tissue-repair process, is highly expressed in several malignant tumors, including pancreatic cancer. We recently showed that CTHRC1 has an important role in the progression and metastasis of pancreatic cancer. Although CTHRC1 secretion affects tumor cells, how it promotes tumorigenesis in the context of the microenvironment is largely unknown. Here we identified a novel role of CTHRC1 as a potent endothelial activator that promotes angiogenesis by recruiting bone marrow-derived cells to the tumor microenvironment during tumorigenesis...
September 30, 2016: Experimental & Molecular Medicine
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