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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
#1
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
#2
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
#3
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
#4
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
#5
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
#6
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...
June 5, 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
#7
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
#8
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
#9
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
#10
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
#11
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
https://www.readbyqxmd.com/read/28545512/tie2-as-a-novel-key-factor-of-microangiopathy-in-systemic-sclerosis
#12
Falk Moritz, Janine Schniering, Jörg H W Distler, Renate E Gay, Steffen Gay, Oliver Distler, Britta Maurer
BACKGROUND: The angiopoietin(Ang)/Tie2 system is a key regulator of vascular biology. The expression of membrane bound (mb) Tie2 and Ang-1 ensures vessel stability, whereas Ang-2, inducible by vascular endothelial growth factor (VEGF), hypoxia, and inflammation, acts as an antagonist. Tie2 signalling is also attenuated by soluble Tie2 (sTie2), the extracellular domain of the receptor, which is shed upon stimulation with VEGF. Herein, we investigate the role of Ang/Tie2 in the peripheral vasculopathy in systemic sclerosis (SSc) including animal models...
May 25, 2017: Arthritis Research & Therapy
https://www.readbyqxmd.com/read/28539655/angiopoietin-1-enhances-neutrophil-chemotaxis-in-vitro-and-migration-in-vivo-through-interaction-with-cd18-and-release-of-ccl4
#13
Amanda Burnett, Ingrid Gomez, David Davila De Leon, Mark Ariaans, Pavlos Progias, Richard A Kammerer, Guillermo Velasco, Marie Marron, Paul Hellewell, Victoria Ridger
Angiopoietins are a family of growth factors that are ligands for the tyrosine kinase receptor, Tie2. Angiopoietin 1 (Ang-1) is agonistic for Tie2, plays a key role in blood vessel maturation and stability and has been shown to possess anti-inflammatory properties. However, Tie2 expression has been demonstrated on human neutrophils and the observation that neutrophils migrate in response to Ang-1 in vitro has confounded research into its exact role in inflammation as well as its potential use as a therapeutic agent...
May 24, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28534941/two-natural-eudesmane-type-sesquiterpenes-from-laggera-alata-inhibit-angiogenesis-and-suppress-breast-cancer-cell-migration-through-vegf-and-angiopoietin-2-mediated-signaling-pathways
#14
Ning Liang, Yaolan Li, Hau Yin Chung
Eudesmane-type sesquiterpenes are natural sesquiterpenes with anti-inflammatory properties, but their anti-angiogenic activities are not known. The present study demonstrated that 5α-hydroxycostic acid and hydroxyisocostic acid, two eudesmane-type sesquiterpenes (ETSs), isolated from the herb Laggera alata, possessed anti-angiogenic effects. Under non-toxic dosage, ETSs suppressed VEGF‑induced proliferation in human umbilical vein endothelial cells (HUVECs) and vessel formation in zebrafish embryos. Moreover, ETSs inhibited VEGF-stimulated HUVEC migration, stress fibers and tube formation...
May 17, 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/28508859/plastic-roles-of-pericytes-in-the-blood-retinal-barrier
#15
Do Young Park, Junyeop Lee, Jaeryung Kim, Kangsan Kim, Seonpyo Hong, Sangyeul Han, Yoshiaki Kubota, Hellmut G Augustin, Lei Ding, Jin Woo Kim, Hail Kim, Yulong He, Ralf H Adams, Gou Young Koh
The blood-retinal barrier (BRB) consists of tightly interconnected capillary endothelial cells covered with pericytes and glia, but the role of the pericytes in BRB regulation is not fully understood. Here, we show that platelet-derived growth factor (PDGF)-B/PDGF receptor beta (PDGFRβ) signalling is critical in formation and maturation of BRB through active recruitment of pericytes onto growing retinal vessels. Impaired pericyte recruitment to the vessels shows multiple vascular hallmarks of diabetic retinopathy (DR) due to BRB disruption...
May 16, 2017: Nature Communications
https://www.readbyqxmd.com/read/28498260/combined-gene-therapy-using-adsvegfr2-and-adstie2-with-chemotherapy-reduces-the-growth-of-human-ovarian-cancer-and-formation-of-ascites-in-mice
#16
Laura Tuppurainen, Hanna Sallinen, Anni Karvonen, Elina Valkonen, Hanne Laakso, Timo Liimatainen, Elisa Hytönen, Kirsi Hämäläinen, Veli-Matti Kosma, Maarit Anttila, Seppo Ylä-Herttuala
OBJECTIVES: Ovarian cancer is highly dependent on tumor microvessels and angiogenesis regulated by vascular endothelial growth factors (VEGFs) and their receptors (VEGFRs) and angiopoietins (Ang) and their Tie receptors. We studied the efficacy of adenoviral (Ad) gene therapy with soluble VEGFR2 and Tie2 combined with paclitaxel and carboplatin for the treatment of ovarian cancer. METHODS: An intraperitoneal human ovarian cancer xenograft model in nude mice (n = 44) was used in this study...
June 2017: International Journal of Gynecological Cancer
https://www.readbyqxmd.com/read/28473437/endothelial-myocyte-enhancer-factor-2c-inhibits-migration-of-smooth-muscle-cells-through-fenestrations-in-the-internal-elastic-lamina
#17
Yao Wei Lu, Anthony M Lowery, Li-Yan Sun, Harold A Singer, Guohao Dai, Alejandro P Adam, Peter A Vincent, John J Schwarz
OBJECTIVE: Laminar flow activates myocyte enhancer factor 2 (MEF2) transcription factors in vitro to induce expression of atheroprotective genes in the endothelium. Here we sought to establish the role of Mef2c in the vascular endothelium in vivo. APPROACH AND RESULTS: To study endothelial Mef2c, we generated endothelial-specific deletion of Mef2c using Tie2-Cre or Cdh5-Cre-ER(T2) and examined aortas and carotid arteries by en face immunofluorescence. We observed enhanced actin stress fiber formation in the Mef2c-deleted thoracic aortic endothelium (laminar flow region), similar to those observed in normal aortic inner curvature (disturbed flow region)...
May 4, 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/28473248/endothelial-deletion-of-mtorc1-protects-against-hindlimb-ischemia-in-diabetic-mice-via-activation-of-autophagy-attenuation-of-oxidative-stress-and-alleviation-of-inflammation
#18
Wensi Fan, Dong Han, Zhongchan Sun, Sai Ma, Lei Gao, Jiangwei Chen, Xiang Li, Xiujuan Li, Miaomiao Fan, Congye Li, Dahai Hu, Yabin Wang, Feng Cao
Peripheral arterial disease (PAD) complicated with diabetes mellitus (DM) still remains a thorny issue due to lack of effective strategies. Our previous study has demonstrated that inhibition of mTORC1 protected adipose-derived stromal cells from hindlimb ischemic injury in PAD mice. However, whether inhibition of mTORC1 could protect against PAD in diabetes mellitus and the underlying mechanisms remained elusive. In this study, we employed endothelial-specific raptor (an essential component of the mTORC1 signaling complex) knockout (KO) mice (Tie2-mTORC1(ko)) to investigate whether and how mTORC1 downregulation could alleviate hindlimb ischemic injury in diabetic mice...
May 1, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28465380/the-angiopoietin-tie2-signaling-axis-in-systemic-inflammation
#19
Samir M Parikh
Systemic inflammation is a hallmark of commonly encountered diseases ranging from bacterial sepsis to sterile syndromes such as major trauma. Derangements in the host vasculature contribute to the cardinal manifestations of sepsis in profound ways. Recent studies of control pathways regulating the vascular endothelium have illuminated how this single cell layer toggles between quiescence and activation to affect the development of shock and multiorgan dysfunction. This article focuses on one such control pathway, the Tie2 receptor and its ligands the angiopoietins, to describe a growing body of genetic, biochemical, mechanistic, and human studies that implicate Tie2 as a critical switch...
May 2, 2017: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/28464467/elevated-expression-of-tie1-is-accompanied-by-acquisition-of-cancer-stemness-properties-in-colorectal-cancer
#20
Miku Torigata, Daishi Yamakawa, Nobuyuki Takakura
The Tie receptors 1 and 2 (Tie1/2) play crucial roles in embryonic angiogenesis. Recent studies suggest enhanced expression of Tie1 in several types of cancer and negative correlations between Tie1 levels and clinical outcome. These observations suggest important functions of Tie1 not only for vascular formation but also in tumorigenesis. Ligands for Tie2, that is angiopoietins 1-4, have been identified, but not for Tie1. To determine the molecular functions of Tie1, its detailed characterization in tumors would be helpful...
June 2017: Cancer Medicine
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