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https://www.readbyqxmd.com/read/28298457/distinct-regulatory-effects-of-myeloid-cell-and-endothelial-cell-nox2-on-blood-pressure
#1
Can Martin Sag, Moritz Schnelle, Juqian Zhang, Colin E Murdoch, Sabine Kossmann, Andrea Protti, Celio X C Santos, Greta J Sawyer, Xiaohong Zhang, Heloise Mongue-Din, Daniel A Richards, Alison C Brewer, Oleksandra Prysyazhna, Lars S Maier, Philip Wenzel, Philip J Eaton, Ajay M Shah
Background -Hypertension due to increased renin angiotensin system (RAS) activation is associated with elevated reactive oxygen species (ROS) production. Previous studies implicate NADPH oxidase (Nox) proteins as important ROS sources during RAS activation, with different Nox isoforms being potentially involved. Among these, Nox2 is expressed in multiple cell types including endothelial cells, fibroblasts, immune cells and microglia. Blood pressure (BP) is regulated at central nervous system, renal and vascular levels but the cell-specific role of Nox2 in BP regulation is unknown...
March 15, 2017: Circulation
https://www.readbyqxmd.com/read/28288344/stereological-and-immunogold-studies-on-tie1-and-tie2-localization-in-glomeruli-indicate-angiopoietin-signaling-in-podocytes
#2
Anastasia Logothetidou, Ward De Spiegelaere, Wim Van den Broeck, Tim Vandecasteele, Liesbeth Couck, Paul Simoens, Pieter Cornillie
Angiopoietins and their TIE receptors are important regulators of vascular stability and remodeling. These molecules are involved not only in the normal development of kidney glomeruli, but also in disease, thus making them promising targets for therapies. Although TIE receptors are mainly found in endothelial cells, some reports observed TIE2 expression in glomerular podocytes as well. This suggests a role of angiopoietins in the regulation of podocytes. In the present study, we aimed to map the subcellular localization of TIE receptors in metanephric glomeruli of fetal pigs using high-resolution immunogold electron microscopy and the relative labeling index stereological approach...
March 2, 2017: Micron: the International Research and Review Journal for Microscopy
https://www.readbyqxmd.com/read/28276491/flunarizine-suppresses-endothelial-angiopoietin-2-in-a-calcium-dependent-fashion-in-sepsis
#3
Jennifer Retzlaff, Kristina Thamm, Chandra C Ghosh, Wolfgang Ziegler, Hermann Haller, Samir M Parikh, Sascha David
Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to an infection leading to systemic inflammation and endothelial barrier breakdown. The vascular-destabilizing factor Angiopoietin-2 (Angpt-2) has been implicated in these processes in humans. Here we screened in an unbiased approach FDA-approved compounds with respect to Angpt-2 suppression in endothelial cells (ECs) in vitro. We identified Flunarizine - a well-known anti-migraine calcium channel (CC) blocker - being able to diminish intracellular Angpt-2 protein in a time- and dose-dependent fashion thereby indirectly reducing the released protein...
March 9, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28248004/highly-efficient-differentiation-of-endothelial-cells-from-pluripotent-stem-cells-requires-the-mapk-and-the-pi3k-pathways
#4
Aja Harding, Elizabeth Cortez-Toledo, Nataly L Magner, Julie R Beegle, Dane P Coleal-Bergum, Dake Hao, Aijun Wang, Jan A Nolta, Ping Zhou
Pluripotent stem cells are a promising source of endothelial cells (ECs) for the treatment of vascular diseases. We have developed a robust protocol to differentiate human induced pluripotent stem cells (hiPSCs) and embryonic stem cells (hESCs) into ECs with high purities (94%-97% CD31(+) and 78%-83% VE-cadherin(+) ) in 8 days without cell sorting. Passaging of these cells yielded a nearly pure population of ECs (99% of CD31(+) and 96.8% VE-cadherin(+) ). These ECs also expressed other endothelial markers vWF, Tie2, NOS3, and exhibited functions of ECs such as uptake of Dil-acetylated low-density lipoprotein and formation of tubes in vitro or vessels in vivo on matrigel...
March 1, 2017: Stem Cells
https://www.readbyqxmd.com/read/28219791/bone-marrow-mesenchymal-stem-cells-conditioned-medium-enhances-vascular-remodeling-after-stroke-in-type-2-diabetic-rats
#5
Jie Xiang, Jinxia Hu, Tong Shen, Bin Liu, Fang Hua, Kun Zan, Jie Zu, Guiyun Cui, Xinchun Ye
Our previous studies have found that stem cells conditioned medium (CM) facilitated functional recovery after stroke in non-diabetics. However, whether bone marrow stromal cells conditioned medium (BMSCs-CM) treatment after stroke in type 2 diabetic (T2DM) rats improve functional outcomes remains unclear. T2DM rats were induced and subjected to stroke then treated with or without BMSCs-CM. Functional outcomes and blood-brain barrier (BBB) leakage were performed, the expression of Angiopoietin (Ang) 1 and tyrosine kinase (Tie) 2 were also assessed...
February 17, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28198371/method-for-dual-viral-vector-mediated-crispr-cas9-gene-disruption-in-primary-human-endothelial-cells
#6
Haixia Gong, Menglin Liu, Jeff Klomp, Bradley J Merrill, Jalees Rehman, Asrar B Malik
Human endothelial cells (ECs) are widely used to study mechanisms of angiogenesis, inflammation, and endothelial permeability. Targeted gene disruption induced by Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)-CRISPR-Associated Protein 9 (Cas9) nuclease gene editing is potentially an important tool for definitively establishing the functional roles of individual genes in ECs. We showed that co-delivery of adenovirus encoding EGFP-tagged Cas9 and lentivirus encoding a single guide RNA (sgRNA) in primary human lung microvascular ECs (HLMVECs) disrupted the expression of the Tie2 gene and protein...
February 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28188225/inflammation-induced-caveolin-1-and-bmprii-depletion-promotes-endothelial-dysfunction-and-tgf%C3%AE-driven-pulmonary-vascular-remodeling
#7
Suellen Darc Santos Oliveira, Maricela Castellon, Jiwang Chen, Marcelo G Bonini, Xiaowu Gu, Michael H Elliott, Roberto F Machado, Richard D Minshall
Endothelial cell (EC) activation and vascular injury are hallmark features of Acute Lung Injury and Acute Respiratory Distress Syndrome (ALI/ARDS). Caveolin-1 (Cav-1) is highly expressed in pulmonary microvascular ECs and plays a key role in maintaining vascular homeostasis. The aim of this study was to determine whether the lung inflammatory response to Escherichia coli lipopolysaccharide (LPS) promotes priming of ECs via Cav-1 depletion and whether this contributes to the onset of pulmonary vascular remodeling...
February 10, 2017: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/28179430/polydom-is-an-extracellular-matrix-protein-involved-in-lymphatic-vessel-remodeling
#8
Nanami Morooka, Sugiko Futaki, Ryoko Sato-Nishiuchi, Masafumi Nishino, Yuta Totani, Chisei Shimono, Itsuko Nakano, Hiroyuki Nakajima, Naoki Mochizuki, Kiyotoshi Sekiguchi
Rationale: Lymphatic vasculature constitutes a second vascular system, essential for immune surveillance and tissue fluid homeostasis. Maturation of the hierarchical vascular structure, with a highly-branched network of capillaries and ducts, is crucial for its function. Environmental cues mediate the remodeling process, but the mechanism that underlies this process is largely unknown. Objective: Polydom (also called Svep1) is an extracellular matrix protein identified as a high-affinity ligand for integrin α9β1...
February 8, 2017: Circulation Research
https://www.readbyqxmd.com/read/28159737/stem-and-progenitor-cell-alterations-in-myelodysplastic-syndromes
#9
Aditi Shastri, Britta Will, Ulrich Steidl, Amit Verma
Recent studies have demonstrated that myelodysplastic syndromes (MDS) arise from a small population of disease initiating hematopoietic stem cells (HSCs) that persist and expand through conventional therapies and are major contributors to disease progression and relapse. MDS stem and progenitor cells are characterized by key founder and driver mutations and are enriched for cytogenetic alterations. Quantitative alterations in stem and progenitor numbers are also seen in a stage specific manner in human MDS samples as well as in murine models of the disease...
February 3, 2017: Blood
https://www.readbyqxmd.com/read/28151770/organ-specific-differences-in-endothelial-permeability-regulating-molecular-responses-in-mouse-and-human-sepsis
#10
Adnan Aslan, Matijs van Meurs, Jill Moser, Eliane R Popa, Rianne M Jongman, Peter J Zwiers, Grietje Molema, Jan G Zijlstra
In patients with sepsis-induced MODS, diverging patterns of oedema formation and loss of function in organs such as lung and kidney suggest that endothelial permeability-regulating molecular responses are differentially regulated. This potential differential regulation has been insufficiently studied at the level of components of adherens and tight junctions. We hypothesized that such a regulation by endothelial cells in sepsis takes place in an organ-specific manner. We addressed our hypothesis by studying by quantitative RT-PCR the expression of a predefined subset of EC permeability-related molecules (occludin, claudin-5, PV-1, CD-31, endomucin, Angiopoietin-1, Angiopoietin-2, Tie2, VEGFA, VEGFR1, VEGFR2, and VE-cadherin) in kidney and lung after systemic LPS injection in mice, and in kidneys of patients who died of sepsis...
February 1, 2017: Shock
https://www.readbyqxmd.com/read/28122355/plumbagin-restrains-hepatocellular-carcinoma-angiogenesis-by-suppressing-the-migration-and-invasion-of-tumor-derived-vascular-endothelial-cells
#11
YanFei Wei, Qi Yang, Yuan Zhang, TieJian Zhao, XueMei Liu, Jing Zhong, Jing Ma, YongXin Chen, Chuan Zhao, JunXuan Li
Tumor occurrence and development are very complicated processes. In addition to the roles of exogenous carcinogenic factors, the body's internal factors also play important roles. These factors include the host response to the tumor and the tumor effect on the host. In particular, the proliferation, migration and activation of endothelial cells are involved in tumor angiogenesis. Angiogenesis is one of the hallmarks of cancer. In this study, we investigate whether plumbagin can abrogate angiogenesis-mediated tumor growth in hepatocellular carcinoma (HCC) and, if so, through which molecular mechanisms...
January 20, 2017: Oncotarget
https://www.readbyqxmd.com/read/28089339/discovery-of-a-murine-model-of-clinical-pah-mission-impossible
#12
REVIEW
Zhiyu Dai, You-Yang Zhao
Pulmonary arterial hypertension (PAH) is a lung vascular disease characterized with a progressive increase of pulmonary vascular resistance and obliterative pulmonary vascular remodeling resulting in right heart failure and premature death. In this brief review, we document the recent advances in identifying genetically modified murine models of PH, with a focus on the recent discovery of the mouse model of Tie2 Cre-mediated deletion of prolyl hydroxylase 2, which exhibits progressive obliterative vascular remodeling, severe PAH, and right heart failure, thus recapitulating many of the features of clinical PAH...
December 15, 2016: Trends in Cardiovascular Medicine
https://www.readbyqxmd.com/read/28079371/binding-pose-flip-explained-via-enthalpic-and-entropic-contributions
#13
Michael Schauperl, Paul Czodrowski, Julian E Fuchs, Roland G Huber, Birgit J Waldner, Maren Podewitz, Christian Kramer, Klaus R Liedl
The anomalous binding modes of five highly similar fragments of TIE2 inhibitors, showing three distinct binding poses, are investigated. We report a quantitative rationalization for the changes in binding pose based on molecular dynamics simulations. We investigated five fragments in complex with the transforming growth factor β receptor type 1 kinase domain. Analyses of these simulations using Grid Inhomogeneous Solvation Theory (GIST), pKA calculations, and a tool to investigate enthalpic differences upon binding unraveled the various thermodynamic contributions to the different binding modes...
February 27, 2017: Journal of Chemical Information and Modeling
https://www.readbyqxmd.com/read/28073001/normalization-of-tumor-vessels-by-tie2-activation-and-ang2-inhibition-enhances-drug-delivery-and-produces-a-favorable-tumor-microenvironment
#14
Jin-Sung Park, Il-Kug Kim, Sangyeul Han, Intae Park, Chan Kim, Jeomil Bae, Seung Ja Oh, Seungjoo Lee, Jeong Hoon Kim, Dong-Cheol Woo, Yulong He, Hellmut G Augustin, Injune Kim, Doheon Lee, Gou Young Koh
No abstract text is available yet for this article.
January 9, 2017: Cancer Cell
https://www.readbyqxmd.com/read/28063039/xenotransplantation-model-of-psoriasis
#15
Jeremy Di Domizio, Curdin Conrad, Michel Gilliet
Psoriasis is a chronic autoimmune skin disease affecting approximately 2 % of the population with a major psychosocial and socioeconomic impact. A causal therapy leading to permanent cure is not available, and current treatments only lead to limited amelioration, and therefore new therapeutic targets need to be identified. Recent works demonstrated a predominant role of TH17 cells in the pathogenesis of psoriasis; yet the underlying molecular mechanisms driving the development of the disease are still largely elusive...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28062977/angiopoietin-pathway-gene-expression-associated-with-poor-breast-cancer-survival
#16
Rajesh Ramanathan, Amy L Olex, Mikhail Dozmorov, Harry D Bear, Leopoldo Jose Fernandez, Kazuaki Takabe
PURPOSE: Angiogenesis is one of the hallmarks of cancer and is essential for cancer progression and metastasis. However, clinical trials with vascular endothelial growth factor (VEGF) pathway inhibitors have failed to show overall survival benefit in breast cancer. Targeted therapy against the angiopoietin pathway, a downstream angiogenesis cascade, could be effective in breast cancer. This study investigates the association of angiopoietin pathway gene expression with breast cancer survival using a "big data" approach employing RNA sequencing data from The Cancer Genome Atlas (TCGA)...
February 2017: Breast Cancer Research and Treatment
https://www.readbyqxmd.com/read/28060852/contribution-of-vascular-cells-to-neointimal-formation
#17
Falei Yuan, Dong Wang, Kang Xu, Jixian Wang, Zhijun Zhang, Li Yang, Guo-Yuan Yang, Song Li
The de-differentiation and proliferation of smooth muscle cells (SMCs) are widely accepted as the major contributor to vascular remodeling. However, recent studies indicate that vascular stem cells (VSCs) also play an important role, but their relative contribution remains to be elucidated. In this study, we used genetic lineage tracing approach to further investigate the contribution of SMCs and VSCs to neointimal thickening in response to endothelium denudation injury or artery ligation. In vitro and in vivo analysis of MYH11-cre/Rosa-loxP-RFP mouse artery showed that SMCs proliferated at a much slower rate than non-SMCs...
2017: PloS One
https://www.readbyqxmd.com/read/28056085/vascular-endothelial-over-expression-of-human-soluble-epoxide-hydrolase-tie2-seh-tr-attenuates-coronary-reactive-hyperemia-in-mice-role-of-oxylipins-and-%C3%AF-hydroxylases
#18
Ahmad Hanif, Matthew L Edin, Darryl C Zeldin, Christophe Morisseau, John R Falck, Mohammed A Nayeem
Cytochromes P450 metabolize arachidonic acid (AA) into two vasoactive oxylipins with opposing biologic effects: epoxyeicosatrienoic acids (EETs) and omega-(ω)-terminal hydroxyeicosatetraenoic acids (HETEs). EETs have numerous beneficial physiological effects, including vasodilation and protection against ischemia/reperfusion injury, whereas ω-terminal HETEs induce vasoconstriction and vascular dysfunction. We evaluated the effect of these oxylipins on post-ischemic vasodilation known as coronary reactive hyperemia (CRH)...
2017: PloS One
https://www.readbyqxmd.com/read/28005151/activated-protein-c-binds-directly-to-tie2-possible-beneficial-effects-on-endothelial-barrier-function
#19
Nikita Minhas, Meilang Xue, Christopher J Jackson
Activated protein C (APC) is a natural anticoagulant with strong anti-inflammatory, anti-apoptotic, and barrier stabilizing properties. These cytoprotective properties of APC are thought to be exerted through its pathway involving the binding of APC to endothelial protein C receptor and cleavage of protease-activated receptors. In this study, we found that APC enhanced endothelial barrier integrity via a novel pathway, by binding directly to and activating Tie2, a transmembrane endothelial tyrosine kinase receptor...
December 22, 2016: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/28005008/angiopoietin-receptor-tie2-is-required-for-vein-specification-and-maintenance-via-regulating-coup-tfii
#20
Man Chu, Taotao Li, Bin Shen, Xudong Cao, Haoyu Zhong, Luqing Zhang, Fei Zhou, Wenjuan Ma, Haijuan Jiang, Pancheng Xie, Zhengzheng Liu, Ningzheng Dong, Ying Xu, Yun Zhao, Guoqiang Xu, Peirong Lu, Jincai Luo, Qingyu Wu, Kari Alitalo, Gou Young Koh, Ralf H Adams, Yulong He
Mechanisms underlying the vein development remain largely unknown. Tie2 signaling mediates endothelial cell (EC) survival and vascular maturation and its activating mutations are linked to venous malformations. Here we show that vein formation are disrupted in mouse skin and mesentery when Tie2 signals are diminished by targeted deletion of Tek either ubiquitously or specifically in embryonic ECs. Postnatal Tie2 attenuation resulted in the degeneration of newly formed veins followed by the formation of haemangioma-like vascular tufts in retina and venous tortuosity...
December 22, 2016: ELife
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