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https://www.readbyqxmd.com/read/28742087/type-1-skewed-neuroinflammation-and-vascular-damage-associated-with-orientia-tsutsugamushi-infection-in-mice
#1
Lynn Soong, HeThomas R Shelite, Yan Xing, Harica Kodakandla, Yuejin Liang, Brandon J Trent, Paulina Horton, Kathryn C Smith, Zhenyang Zhao, Jiaren Sun, Donald H Bouyer, Jiyang Cai
BACKGROUND: Scrub typhus is a life-threatening disease, due to infection with O. tsutsugamushi, a Gram-negative bacterium that preferentially replicates in endothelial cells and professional phagocytes. Meningoencephalitis has been reported in scrub typhus patients and experimentally-infected animals; however, the neurological manifestation and its underlying mechanisms remain poorly understood. To address this issue, we focused on Orientia tsutsugamushi Karp strain (OtK), and examined host responses in the brain during lethal versus self-healing scrub typhus disease in our newly established murine models...
July 24, 2017: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/28727816/high-levels-of-flt3-ligand-in-bone-marrow-and-peripheral-blood-of-patients-with-advanced-multiple-myeloma
#2
Normann Steiner, Roman Hajek, Sabina Sevcikova, Bojana Borjan, Karin Jöhrer, Georg Göbel, Gerold Untergasser, Eberhard Gunsilius
INTRODUCTION: Multiple myeloma (MM) is still incurable due to resistance against various therapies. Thus, the identification of biomarkers predicting progression is urgently needed. Here, we evaluated four biomarkers in bone marrow and peripheral blood of MM patients for their prognostic significance. MATERIALS & METHODS: Bone marrow- and peripheral blood plasma levels of FLT3-L, soluble TIE2, endostatin, and osteoactivin were determined in patients with monoclonal gammopathy of undetermined significance (MGUS, n = 14/n = 4), patients with newly diagnosed MM (NDMM, n = 42/n = 31) and patients with relapsed/refractory MM (RRMM, n = 27/n = 16) by sandwich ELISA...
2017: PloS One
https://www.readbyqxmd.com/read/28719646/a-synergistic-negative-effect-of-gestational-smoke-exposure-and-small-litter-size-on-rat-placental-efficiency-vascularisation-and-angiogenic-factors-mrna-expression
#3
Zhen-Yan Chen, Ying Yao
Smoking increases the risk of pregnancy complications such as spontaneous abortion and low birth weight (LBW). By cigarette smoke exposure (gestational day, GD3-17), normal-litter-size pregnancy with low birth weight (NP-LBW) and small-litter-size pregnancy with normal birth weight (SP-NBW) in rats were induced. The placental weight in SP-NBW was twice the weight of the normal in contrast with the smaller placenta in NP-LBW. Compared with the normal, placental efficiency (expressed as fetus-to-placenta weight ratio) and placental vascularisation were significantly decreased in smoke exposed placentas with more obvious decrease in SP-NBW...
2017: PloS One
https://www.readbyqxmd.com/read/28719590/pericyte-expressed-tie2-controls-angiogenesis-and-vessel-maturation
#4
Martin Teichert, Laura Milde, Annegret Holm, Laura Stanicek, Nicolas Gengenbacher, Soniya Savant, Tina Ruckdeschel, Zulfiyya Hasanov, Kshitij Srivastava, Junhao Hu, Stella Hertel, Arne Bartol, Katharina Schlereth, Hellmut G Augustin
The Tie receptors with their Angiopoietin ligands act as regulators of angiogenesis and vessel maturation. Tie2 exerts its functions through its supposed endothelial-specific expression. Yet, Tie2 is also expressed at lower levels by pericytes and it has not been unravelled through which mechanisms pericyte Angiopoietin/Tie signalling affects angiogenesis. Here we show that human and murine pericytes express functional Tie2 receptor. Silencing of Tie2 in pericytes results in a pro-migratory phenotype. Pericyte Tie2 controls sprouting angiogenesis in in vitro sprouting and in vivo spheroid assays...
July 18, 2017: Nature Communications
https://www.readbyqxmd.com/read/28705792/deletion-of-fstl1-follistatin-like-1-from-the-endocardial-endothelial-lineage-causes-mitral-valve-disease
#5
Stuti Prakash, Luis J J Borreguero, Marc Sylva, Lorena Flores Ruiz, Fereshte Rezai, Quinn D Gunst, José-Luis de la Pompa, Jan M Ruijter, Maurice J B van den Hoff
OBJECTIVE: Fstl1 (Follistatin-like 1) is a secreted protein that is expressed in the atrioventricular valves throughout embryonic development, postnatal maturation, and adulthood. In this study, we investigated the loss of Fstl1 in the endocardium/endothelium and their derived cells. APPROACH AND RESULTS: We conditionally ablated Fstl1 from the endocardial lineage using a transgenic Tie2-Cre mouse model. These mice showed a sustained Bmp and Tgfβ signaling after birth...
July 13, 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/28695891/the-endothelial-transcription-factor-erg-mediates-angiopoietin-1-dependent-control-of-notch-signalling-and-vascular-stability
#6
A V Shah, G M Birdsey, C Peghaire, M E Pitulescu, N P Dufton, Y Yang, I Weinberg, L Osuna Almagro, L Payne, J C Mason, H Gerhardt, R H Adams, A M Randi
Notch and Angiopoietin-1 (Ang1)/Tie2 pathways are crucial for vascular maturation and stability. Here we identify the transcription factor ERG as a key regulator of endothelial Notch signalling. We show that ERG controls the balance between Notch ligands by driving Delta-like ligand 4 (Dll4) while repressing Jagged1 (Jag1) expression. In vivo, this regulation occurs selectively in the maturing plexus of the mouse developing retina, where Ang1/Tie2 signalling is active. We find that ERG mediates Ang1-dependent regulation of Notch ligands and is required for the stabilizing effects of Ang1 in vivo...
July 11, 2017: Nature Communications
https://www.readbyqxmd.com/read/28680581/endothelial-follistatin-like-1-regulates-the-postnatal-development-of-the-pulmonary-vasculature-by-modulating-bmp-smad-signaling
#7
Navessa P Tania, Harm Maarsingh, I Sophie T Bos, Andrea Mattiotti, Stuti Prakash, Wim Timens, Quinn D Gunst, Luis J Jimenez-Borreguero, Martina Schmidt, Maurice J B van den Hoff, Reinoud Gosens
Bone morphogenetic protein (BMP) signaling regulates vascular smooth muscle maturation, endothelial cell proliferation, and tube formation. The endogenous BMP antagonist Follistatin-like 1 (Fstl1) is highly expressed in pulmonary vascular endothelium of the developing mouse lung, suggesting a role in pulmonary vascular formation and vascular homeostasis. The aim of this study was to investigate the role of Fstl1 in the pulmonary vascular endothelium. To this aim, Fstl1 was conditionally deleted from endothelial and endothelial-derived cells using Tie2-cre driven Fstl1-KO mice (Fstl1-eKO mice)...
March 2017: Pulmonary Circulation
https://www.readbyqxmd.com/read/28679654/neoadjuvant-chemotherapy-induces-breast-cancer-metastasis-through-a-tmem-mediated-mechanism
#8
George S Karagiannis, Jessica M Pastoriza, Yarong Wang, Allison S Harney, David Entenberg, Jeanine Pignatelli, Ved P Sharma, Emily A Xue, Esther Cheng, Timothy M D'Alfonso, Joan G Jones, Jesus Anampa, Thomas E Rohan, Joseph A Sparano, John S Condeelis, Maja H Oktay
Breast cancer cells disseminate through TIE2/MENA(Calc)/MENA(INV)-dependent cancer cell intravasation sites, called tumor microenvironment of metastasis (TMEM), which are clinically validated as prognostic markers of metastasis in breast cancer patients. Using fixed tissue and intravital imaging of a PyMT murine model and patient-derived xenografts, we show that chemotherapy increases the density and activity of TMEM sites and Mena expression and promotes distant metastasis. Moreover, in the residual breast cancers of patients treated with neoadjuvant paclitaxel after doxorubicin plus cyclophosphamide, TMEM score and its mechanistically connected MENA(INV) isoform expression pattern were both increased, suggesting that chemotherapy, despite decreasing tumor size, increases the risk of metastatic dissemination...
July 5, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28676569/vegf-a-and-neuropilin-1-nrp1-shape-axon-projections-in-the-developing-cns-via-dual-roles-in-neurons-and-blood-vessels
#9
Lynda Erskine, Urielle François, Laura Denti, Andy Joyce, Miguel Tillo, Freyja Bruce, Neil Vargesson, Christiana Ruhrberg
Visual information is relayed from the eye to the brain via retinal ganglion cell (RGC) axons. Mice lacking NRP1 or NRP1-binding VEGF-A isoforms have defective RGC axon organisation alongside brain vascular defects. It is not known whether axonal defects are caused exclusively by defective VEGF-A signalling in RGCs or are exacerbated by abnormal vascular morphology. Targeted NRP1 ablation in RGCs with a Brn3b(Cre) knock-in allele reduced axonal midline crossing at the optic chiasm and optic tract fasciculation...
July 1, 2017: Development
https://www.readbyqxmd.com/read/28637680/myoendothelial-gap-junctions-mediate-regulation-of-angiopoietin-2-induced-vascular-hyporeactivity-after-hypoxia-through-connexin-43-gated-camp-transfer
#10
Jing Xu, Guang-Ming Yang, Tao Li, Liang-Ming Liu
Angiopoietin-2 (Ang2) contributes to vascular hyporeactivity after hemorrhagic shock and hypoxia through upregulation of inducible nitric oxide synthase (iNOS), in a vascular endothelial cell (VEC)-specific and Ang2/Tie2 receptor-dependent manner. While iNOS is primarily expressed in vascular smooth muscle cells (VSMCs), the mechanisms of signal transfer from VECs to VSMCs are unknown. A double-sided co-culture model with VECs and VSMCs from Sprague Dawley rats was used to investigate the role of myoendothelial gap junctions (MEGJs), the connexin (Cx) isoforms involved and other relevant mechanisms...
June 21, 2017: American Journal of Physiology. Cell Physiology
https://www.readbyqxmd.com/read/28623351/regulation-of-angiopoietin-signalling-by-soluble-tie2-ectodomain-and-engineered-ligand-trap
#11
Deborah O A Alawo, Tariq A Tahir, Marlies Fischer, Declan G Bates, Svetlana R Amirova, Nicholas P J Brindle
Angiopoietin-1 (Angpt1) is a glycoprotein ligand important for maintaining the vascular system. It signals via a receptor tyrosine kinase expressed on the surface on endothelial cells, Tie2. This receptor can undergo regulated ectodomain cleavage that releases the ligand-binding domain (sTie2) into the circulation. The concentration of sTie2 is increased in a range of conditions, including peripheral arterial disease and myocardial infarction, where it has been suggested to bind and block Angpt1 resulting in vascular dysfunction...
June 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28601681/mutation-of-angiopoietin-1-gene-associates-with-a-new-type-of-hereditary-angioedema
#12
Valeria Bafunno, Davide Firinu, Maria D'Apolito, Giorgia Cordisco, Stefania Loffredo, Angelica Leccese, Maria Bova, Maria Pina Barca, Rosa Santacroce, Marco Cicardi, Stefano Del Giacco, Maurizio Margaglione
BACKGROUND: Hereditary angioedema (HAE) is a rare genetic disease usually due to mutation within the C1 inhibitor or the coagulation Factor XII gene. However, in a series of patients with HAE no causative variants have been described and the pathophysiology of the disease remains unknown (U-HAE). Identification of causative genes in U-HAE is valuable for understanding the cause of the disease. OBJECTIVE: We conducted genetic studies in Italian patients with U-HAE to identify novel causative genes...
June 7, 2017: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/28587659/glutaminyl-cyclase-activity-correlates-with-levels-of-a%C3%AE-peptides-and-mediators-of-angiogenesis-in-cerebrospinal-fluid-of-alzheimer-s-disease-patients
#13
Claire Bridel, Torsten Hoffmann, Antje Meyer, Sisi Durieux, Marleen A Koel-Simmelink, Matthias Orth, Philip Scheltens, Inge Lues, Charlotte E Teunissen
BACKGROUND: Pyroglutamylation of truncated Aβ peptides, which is catalysed by enzyme glutaminyl cyclase (QC), generates pE-Aβ species with enhanced aggregation propensities and resistance to most amino-peptidases and endo-peptidases. pE-Aβ species have been identified as major constituents of Aβ plaques and reduction of pE-Aβ species is associated with improvement of cognitive tasks in animal models of Alzheimer's disease (AD). Pharmacological inhibition of QC has thus emerged as a promising therapeutic approach for AD...
June 6, 2017: Alzheimer's Research & Therapy
https://www.readbyqxmd.com/read/28586644/endothelial-to-osteoblast-conversion-generates-osteoblastic-metastasis-of-prostate-cancer
#14
Song-Chang Lin, Yu-Chen Lee, Guoyu Yu, Chien-Jui Cheng, Xin Zhou, Khoi Chu, Monzur Murshed, Nhat-Tu Le, Laura Baseler, Jun-Ichi Abe, Keigi Fujiwara, Benoit deCrombrugghe, Christopher J Logothetis, Gary E Gallick, Li-Yuan Yu-Lee, Sankar N Maity, Sue-Hwa Lin
Prostate cancer (PCa) bone metastasis is frequently associated with bone-forming lesions, but the source of the osteoblastic lesions remains unclear. We show that the tumor-induced bone derives partly from tumor-associated endothelial cells that have undergone endothelial-to-osteoblast (EC-to-OSB) conversion. The tumor-associated osteoblasts in PCa bone metastasis specimens and patient-derived xenografts (PDXs) were found to co-express endothelial marker Tie-2. BMP4, identified in PDX-conditioned medium, promoted EC-to-OSB conversion of 2H11 endothelial cells...
June 5, 2017: Developmental Cell
https://www.readbyqxmd.com/read/28584011/regulatory-t-cell-augmentation-or-interleukin-17-inhibition-prevents-calcineurin-inhibitor-induced-hypertension-in-mice
#15
Valorie L Chiasson, Abhinandan R Pakanati, Marcos Hernandez, Kristina J Young, Kelsey R Bounds, Brett M Mitchell
The immunosuppressive calcineurin inhibitors cyclosporine A and tacrolimus alter T-cell subsets and can cause hypertension, vascular dysfunction, and renal toxicity. We and others have reported that cyclosporine A and tacrolimus decrease anti-inflammatory regulatory T cells and increase proinflammatory interleukin-17-producing T cells; therefore, we hypothesized that inhibition of these effects using noncellular therapies would prevent the hypertension, endothelial dysfunction, and renal glomerular injury induced by calcineurin inhibitor therapy...
July 2017: Hypertension
https://www.readbyqxmd.com/read/28583105/characteristics-and-potentials-of-stem-cells-derived-from-human-degenerated-nucleus-pulposus-potential-for-regeneration-of-the-intervertebral-disc
#16
Xiao-Chuan Li, Yong Tang, Jian-Hong Wu, Pu-Shan Yang, De-Li Wang, Di-Ke Ruan
BACKGROUND: Eliminating the symptoms during treatment of intervertebral disc degeneration (IVDD) is only a temporary solution that does not cure the underlying cause. A biological method to treat this disorder may be possible by the newly discovered nucleus pulposus derived stem cells (NPDCs). However, the uncertain characteristics and potential of NPDCs calls for a comprehensive study. METHODS: In the present study, nucleus pulposus samples were obtained from 5 patients with IVDD undergoing discectomy procedure and NPDCs were harvested using fluorescence activated cell sorting (FACS) by the co-expression of GD2(+) and Tie2(+)...
June 5, 2017: BMC Musculoskeletal Disorders
https://www.readbyqxmd.com/read/28582314/angiopoietins-and-tie2-in-vascular-inflammation
#17
Samir M Parikh
PURPOSE OF REVIEW: As a subset of the organism-wide reaction to severe infection, the host vascular response has received increasing attention in recent years. The transformation that small blood vessels undergo to facilitate the clearance of pathogens may become harmful to the host if it occurs too broadly or if it is sustained too long. Adverse clinical manifestations of leaky and inflamed blood vessels include edema impairing the function of critical organs and circulatory shock. RECENT FINDINGS: The study suggests that this host vascular response may be both measurable and potentially targetable...
June 2, 2017: Current Opinion in Hematology
https://www.readbyqxmd.com/read/28576878/the-disulfide-isomerase-erp72-supports-arterial-thrombosis-in-mice
#18
Junsong Zhou, Yi Wu, Fengwu Chen, Lu Wang, Lubica Rauova, Vincent M Hayes, Mortimer Poncz, Hong Li, Tong Liu, Junling Liu, David W Essex
Several CGHC motif-containing disulfide isomerases support thrombosis. We here report that ERp72, with three CGHC redox-active sites (a(o), a, and a'), supports thrombosis. We generated a new conditional knockout mouse model, and found that Tie2-Cre/ERp72(fl/fl) mice with blood and endothelial cells lacking ERp72 had prolonged tail bleeding times, and decreased platelet accumulation in laser-induced cremaster arteriole injury and FeCl3-induced mesenteric arterial injury. Fibrin deposition was decreased in the laser injury model...
June 2, 2017: Blood
https://www.readbyqxmd.com/read/28562653/correction-constitutive-association-of-tie1-and-tie2-with-endothelial-integrins-is-functionally-modulated-by-angiopoietin-1-and-fibronectin
#19
Annamarie C Dalton, Tomer Shlamkovitch, Niv Papo, William A Barton
[This corrects the article DOI: 10.1371/journal.pone.0163732.].
2017: PloS One
https://www.readbyqxmd.com/read/28550640/endogenous-tissue-factor-pathway-inhibitor-in-vascular-smooth-muscle-cells-inhibits-arterial-thrombosis
#20
Jichun Yang, Kaiyue Jin, Jiajun Xiao, Jing Ma, Duan Ma
Tissue factor pathway inhibitor (TFPI) is the main inhibitor of tissue factor-mediated coagulation. TFPI is expressed by endothelial and smooth muscle cells in the vasculature. Endothelium-derived TFPI has been reported to play a regulatory role in arterial thrombosis. However, the role of endogenous TFPI in vascular smooth muscle cells (VSMCs) in thrombosis and vascular disease development has yet to be elucidated. In this TFPI(Flox) mice crossbred with Sma-Cre mice were utilized to establish TFPI conditional knockout mice and to examine the effects of VSMC-directed TFPI deletion on development, hemostasis, and thrombosis...
May 27, 2017: Frontiers of Medicine
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