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Start Over Descriptor "MESH : Neovascularization, Physiologic" Topic angiogenesis
5 results on '"MESH : Neovascularization, Physiologic"'

1. Interaction of the coiled‐coil domain with glycosaminoglycans protects angiopoietin‐like 4 from proteolysis and regulates its antiangiogenic activity

Author

Sylvie Ricard-Blum, Clément Faye, Corinne Ardidie-Robouant, Clémence Chomel, Laurent Muller, Stéphane Germain, Aurélie Cazes, A. Barret, Catherine Monnot, Elisa Gomez, Marine Bignon, Pathologie vasculaire et endocrinologie rénale - Chaire de médecine expérimentale (INSERM U36), Collège de France (CdF (institution))-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'anatomo-pathologie [CHU HEGP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Institut de biologie et chimie des protéines [Lyon] (IBCP), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Centre interdisciplinaire de recherche en biologie (CIRB), Labex MemoLife, École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Collège de France (CdF (institution))-Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), Université Paris sciences et lettres (PSL)-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), This work was supported by the European Vascular Genomics Network (http://www.evgn.org) (contract LSHMCT-2003-503254), ANR-06-JCJC-0160,ANGPTL4,Role of ANGPTL4 during development and ischemic heart disease(2006), Pathologie vasculaire et endocrinologie rénale, Collège de France ( CdF ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Experimental Medicine Unit, Collège de France ( CdF ), Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Européen Georges Pompidou [APHP] ( HEGP ), Institut de biologie et chimie des protéines [Lyon] ( IBCP ), Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique ( CNRS ), Service d'hématologie A [CHU HEGP], and ANR-06-JCJC-0160,ANGPTL4,Role of ANGPTL4 during development and ischemic heart disease ( 2006 )

Subjects
MESH : Cell Line, MESH : Angiopoietins, Protein Conformation, Angiogenesis, MESH: Cricetinae, Biochemistry, Extracellular matrix, angiogenesis, MESH: Protein Structure, Tertiary, MESH: Protein Conformation, 0302 clinical medicine, MESH : Lipid Metabolism, Cricetinae, MESH: Animals, MESH : Protein Conformation, Glycosaminoglycans, MESH: Lipid Metabolism, 0303 health sciences, MESH : Neovascularization, Physiologic, medicine.diagnostic_test, Chemistry, MESH : Cricetinae, MESH : Extracellular Matrix, MESH : Protein Binding, MESH: Glycosaminoglycans, [ SDV.MHEP.CSC ] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, 3. Good health, Cell biology, Endothelial stem cell, 030220 oncology & carcinogenesis, endothelial cell, MESH : Mutation, MESH : Protein Structure, Tertiary, MESH: Neovascularization, Physiologic, Protein Binding, Biotechnology, MESH: Mutation, extracellular matrix, Proteolysis, Neovascularization, Physiologic, Angiopoietin-like 4 Protein, MESH: Extracellular Matrix, Cell Line, Angiopoietin, 03 medical and health sciences, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, MESH : Glycosaminoglycans, Genetics, medicine, Animals, Humans, MESH: Protein Binding, Molecular Biology, 030304 developmental biology, MESH: Humans, hypoxia, MESH : Humans, Lipid Metabolism, Protein Structure, Tertiary, MESH: Cell Line, Cell culture, MESH: Angiopoietins, Mutation, MESH : Animals, Proprotein Convertases, Angiopoietins
Abstract

International audience; Angiopoietin-like 4 (ANGPTL4) is involved in angiogenesis and lipid metabolism. It is secreted by liver and adipose tissues and cleaved to generate circulating coiled-coil domain (CCD) and fibrinogen-like domain (FLD) fragments. The full-length ANGPTL4 produced by hypoxic endothelial cells interacts with the extracellular matrix (ECM). The ECM-bound and soluble forms of ANGPTL4 have antiangiogenic properties. We carried out a structure-function analysis to investigate the regulation of ANGPTL4 bioactivity in endothelial cells. We found that the recombinant CCD binds to the ECM, whereas the FLD is released into the medium. The CCD, like the full-length ANGPTL4, binds to heparan and dermatan sulfates in surface plasmon resonance assays and inhibits endothelial cell adhesion, motility, and tubule-like formation. In endothelial cells, ANGPTL4 is processed in the secretion medium after release from the ECM. This processing is altered by the proprotein convertases inhibitor alpha1-PDX and abolished by the mutation of the (161)RRKR(164) cleavage site without modification of the ECM binding and release. These data suggest that the full-length form, which interacts with heparan sulfate proteoglycans via its CCD, is protected from proteolysis by proprotein convertases and constitutes the major active pool of ANGPTL4 in hypoxic endothelial cells.

Published
2008
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2. Inhibition of prolyl hydroxylase domain proteins promotes therapeutic revascularization

Author

Jacques Pouysségur, Amandine Ginouvès, Bernard I. Levy, Micheline Duriez, Jean-Sébastien Silvestre, Edurne Berra, José Vilar, Alice Recalde, Yasmine Zouggari, Céline Loinard, Clément Cochain, Institut de signalisation, biologie du développement et cancer (ISBDC), Centre National de la Recherche Scientifique (CNRS)-Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Université Côte d'Azur (UCA), Paris-Centre de Recherche Cardiovasculaire (PARCC - UMR-S U970), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Institut de signalisation, biologie du développement et cancer ( ISBDC ), Université Nice Sophia Antipolis ( UNS ), Université Côte d'Azur ( UCA ) -Université Côte d'Azur ( UCA ) -Centre National de la Recherche Scientifique ( CNRS ), Paris-Centre de Recherche Cardiovasculaire ( PARCC - U970 ), Hôpital Européen Georges Pompidou [APHP] ( HEGP ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Laboratoire de génétique et biologie cellulaire ( LGBC ), Université de Versailles Saint-Quentin-en-Yvelines ( UVSQ ) -École pratique des hautes études ( EPHE ) -Centre National de la Recherche Scientifique ( CNRS ), Université Nice Sophia Antipolis (... - 2019) (UNS), Université Côte d'Azur (UCA)-Université Côte d'Azur (UCA)-Centre National de la Recherche Scientifique (CNRS), Université Paris Descartes - Paris 5 (UPD5)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire de génétique et biologie cellulaire (LGBC), and Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-École pratique des hautes études (EPHE)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Vascular Endothelial Growth Factor A, MESH: Inflammation, MESH: Signal Transduction, Pathology, MESH : RNA, Messenger, Angiogenesis, Small hairpin RNA, Neovascularization, Mice, 0302 clinical medicine, Ischemia, Medicine, MESH: Animals, MESH: Gene Silencing, [SDV.BDD]Life Sciences [q-bio]/Development Biology, MESH : Macrophages, 0303 health sciences, MESH : Neovascularization, Physiologic, MESH : Procollagen-Proline Dioxygenase, MESH: Hindlimb, MESH: Chemokines, Cell biology, Hindlimb, Femoral Artery, medicine.anatomical_structure, 030220 oncology & carcinogenesis, MESH : Vascular Endothelial Growth Factor A, medicine.symptom, Chemokines, Cardiology and Cardiovascular Medicine, MESH : Gene Therapy, MESH: Neovascularization, Physiologic, MESH: Nitric Oxide Synthase Type III, Plasmids, Signal Transduction, MESH: Femoral Artery, MESH: Procollagen-Proline Dioxygenase, medicine.medical_specialty, MESH : Hypoxia-Inducible Factor 1, alpha Subunit, Nitric Oxide Synthase Type III, Procollagen-Proline Dioxygenase, MESH : Femoral Artery, Neovascularization, Physiologic, MESH : Mice, Inbred C57BL, MESH : Nitric Oxide Synthase Type III, MESH: Hypoxia-Inducible Factor 1, alpha Subunit, Hypoxia-Inducible Factor-Proline Dioxygenases, 03 medical and health sciences, Downregulation and upregulation, MESH : Ischemia, MESH: Mice, Inbred C57BL, MESH: Plasmids, Physiology (medical), MESH : Mice, MESH : Gene Silencing, Gene silencing, Animals, MESH : Chemokines, [ SDV.BDD ] Life Sciences [q-bio]/Development Biology, Gene Silencing, RNA, Messenger, Transcription factor, MESH: Mice, 030304 developmental biology, MESH: RNA, Messenger, MESH : Signal Transduction, Inflammation, Messenger RNA, MESH : Hindlimb, MESH : Inflammation, business.industry, Monocyte, Macrophages, MESH: Vascular Endothelial Growth Factor A, MESH: Macrophages, Genetic Therapy, Hypoxia-Inducible Factor 1, alpha Subunit, Mice, Inbred C57BL, MESH : Plasmids, MESH : Animals, MESH: Gene Therapy, MESH: Ischemia, business
Abstract

Background— The hypoxia-inducible transcription factor (HIF) subunits are destabilized via the O 2 -dependent prolyl hydroxylase domain proteins (PHD1, PHD2, and PHD3). We investigated whether inhibition of PHDs via upregulating HIF might promote postischemic neovascularization. Methods and Results— Mice with right femoral artery ligation were treated, by in vivo electrotransfer, with plasmids encoding for an irrelevant short hairpin RNA (shRNA) (shCON [control]) or specific shRNAs directed against HIF-1α (shHIF-1α), PHD1 (shPHD1), PHD2 (shPHD2), and PHD3 (shPHD3). The silencing of PHDs induced a specific and transient downregulation of their respective mRNA and protein levels at day 2 after ischemia and, as expected, upregulated HIF-1α. As a consequence, 2 key hypoxia-inducible proangiogenic actors, vascular endothelial growth factor-A and endothelial nitric oxide synthase, were upregulated at the mRNA and protein levels. In addition, monocyte chemotactic protein-1 mRNA levels and infiltration of Mac-3-positive macrophages were enhanced in ischemic leg of mice treated with shPHD2 and shPHD3. Furthermore, activation of HIF-1α-related pathways was associated with changes in postischemic neovascularization. At day 14, silencing of PHD2 and PHD3 increased vessel density by 2.2- and 2.6-fold, capillary density by 1.8- and 2.1-fold, and foot perfusion by 1.2- and 1.4-fold, respectively, compared with shCON ( P Conclusions— We demonstrated that a direct inhibition of PHDs, and more particularly PHD3, promoted therapeutic revascularization. Furthermore, we showed that activation of the HIF-1 signaling pathway is required to promote this revascularization.

Published
2009
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3. Microparticles from ischemic muscle promotes postnatal vasculogenesis

Author

Jean-Sébastien Silvestre, José Vilar, Giovanna Chimini, Alain Tedgui, Téni G. Ebrahimian, Aurélie S. Leroyer, Bernard I. Levy, Clément Cochain, Olivier Blanc-Brude, Chantal M. Boulanger, Barend Mees, Alice Recalde, Paris-Centre de Recherche Cardiovasculaire (PARCC - U970), Université Paris Descartes - Paris 5 (UPD5) - Institut National de la Santé et de la Recherche Médicale (INSERM) - Hôpital Européen Georges Pompidou [APHP] (HEGP), Departments of Vascular Surgery and of Cell Biology and Genetics Erasmus, University Medical Center, Centre d'Immunologie de Marseille - Luminy (CIML), Aix Marseille Université (AMU) - Institut National de la Santé et de la Recherche Médicale (INSERM) - Centre National de la Recherche Scientifique (CNRS), Paris-Centre de Recherche Cardiovasculaire (PARCC - UMR-S U970), Université Paris Descartes - Paris 5 (UPD5)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Institut National de la Santé et de la Recherche Médicale (INSERM), VU University Medical Center [Amsterdam], Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU), Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)

Subjects
MESH: Annexin A5, Angiogenesis, MESH: Membrane Glycoproteins, MESH: Cell Hypoxia, MESH : Reactive Oxygen Species, MESH : Cell-Derived Microparticles, MESH : Membrane Glycoproteins, 030204 cardiovascular system & hematology, MESH: Mice, Knockout, Neovascularization, Mice, 0302 clinical medicine, Annexin, Cell-Derived Microparticles, Ischemia, MESH: Cell-Derived Microparticles, MESH: Animals, MESH: Endothelial Cells, Annexin A5, MESH: NADPH Oxidase, MESH : Ligation, MESH : Muscle, Skeletal, Mice, Knockout, MESH: Muscle, Skeletal, 0303 health sciences, Membrane Glycoproteins, MESH : Neovascularization, Physiologic, Hematopoietic Stem Cell Transplantation, MESH: Reactive Oxygen Species, Cell Differentiation, Cell Hypoxia, Femoral Artery, medicine.anatomical_structure, Enzyme Induction, NADPH Oxidase 2, MESH: ATP-Binding Cassette Transporters, [SDV.IMM]Life Sciences [q-bio]/Immunology, MESH : Cell Hypoxia, MESH: Endothelium, Vascular, medicine.symptom, Cardiology and Cardiovascular Medicine, MESH : Cell Differentiation, MESH: Neovascularization, Physiologic, MESH: Femoral Artery, ATP Binding Cassette Transporter 1, MESH: Cell Differentiation, medicine.medical_specialty, congenital, hereditary, and neonatal diseases and abnormalities, MESH: Enzyme Induction, Endothelium, [SDV.IMM] Life Sciences [q-bio]/Immunology, Neovascularization, Physiologic, MESH : Femoral Artery, 03 medical and health sciences, Vasculogenesis, MESH : NADPH Oxidase, MESH : Ischemia, Physiology (medical), Internal medicine, MESH : Hematopoietic Stem Cell Transplantation, MESH : Mice, medicine, Animals, Humans, MESH : ATP-Binding Cassette Transporters, Progenitor cell, Muscle, Skeletal, MESH: Mice, Ligation, MESH: Hematopoietic Stem Cell Transplantation, 030304 developmental biology, MESH: Humans, business.industry, MESH : Endothelial Cells, MESH : Enzyme Induction, MESH : Humans, Endothelial Cells, NADPH Oxidases, MESH: Ligation, medicine.disease, Transplantation, Endocrinology, MESH : Endothelium, Vascular, Immunology, MESH : Mice, Knockout, ATP-Binding Cassette Transporters, Endothelium, Vascular, MESH : Animals, MESH: Ischemia, business, Reactive Oxygen Species, MESH : Annexin A5
Abstract

Background— We hypothesized that microparticles (MPs) released after ischemia are endogenous signals leading to postischemic vasculogenesis. Methods and Results— MPs from mice ischemic hind-limb muscle were detected by electron microscopy 48 hours after unilateral femoral artery ligation as vesicles of 0.1- to 1-μm diameter. After isolation by sequential centrifugation, flow cytometry analyses showed that the annexin V + MP concentration was 3.5-fold higher in ischemic calves than control muscles (1392±406 versus 394±180 annexin V + MPs per 1 mg; P 144+ ). MPs isolated from ischemic muscles induced more potent in vitro bone marrow–mononuclear cell (BM-MNC) differentiation into cells with endothelial phenotype than those isolated from control muscles. MPs isolated from atherosclerotic plaques were ineffective, whereas those isolated from apoptotic or interleukin-1β–activated endothelial cells also promoted BM-MNC differentiation. Interestingly, MPs from ischemic muscles produced more reactive oxygen species and expressed significantly higher levels of NADPH oxidase p47 (6-fold; P P P Conclusion— MPs produced during tissue ischemia stimulate progenitor cell differentiation and subsequently promote postnatal neovascularization.

Published
2009
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4. Extracellular matrix-bound angiopoietin-like 4 inhibits endothelial cell adhesion, migration, and sprouting and alters actin cytoskeleton

Author

Nicolas Bréchot, Ariane Galaup, Clémence Chomel, Laurent Muller, Marine Bignon, Stéphane Germain, Catherine Monnot, Pierre Corvol, Aurélie Cazes, Holger Weber, Sébastien Le Jan, Pathologie vasculaire et endocrinologie rénale - Chaire de médecine expérimentale (INSERM U36), Collège de France (CdF (institution))-Institut National de la Santé et de la Recherche Médicale (INSERM), Departement of Vascular Biology and Angiogenesis Research, Tumor Biology Center, Centre interdisciplinaire de recherche en biologie (CIRB), Labex MemoLife, École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Collège de France (CdF (institution))-Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), Université Paris sciences et lettres (PSL)-École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Mouret, Sandrine, École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Pathologie vasculaire et endocrinologie rénale, Collège de France ( CdF ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Service d'hématologie A [CHU HEGP], and Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Européen Georges Pompidou [APHP] ( HEGP )

Subjects
MESH: Heparin, MESH : Biological Availability, Physiology, Angiogenesis, MESH: Anoxia, MESH : Actins, Extracellular matrix, MESH : Cytoskeleton, Mice, 0302 clinical medicine, Cell Movement, Ischemia, MESH: Blood Proteins, MESH : Cell Movement, MESH: Animals, MESH: Endothelial Cells, Hypoxia, Cytoskeleton, MESH: Cell Movement, Cells, Cultured, MESH: Biological Availability, Tube formation, 0303 health sciences, MESH : Neovascularization, Physiologic, MESH: Hindlimb, MESH : Extracellular Matrix, Blood Proteins, [ SDV.MHEP.CSC ] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, MESH : Proteoglycans, Extracellular Matrix, Hindlimb, Cell biology, [SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Endothelial stem cell, Biochemistry, 030220 oncology & carcinogenesis, MESH: Proteoglycans, Proteoglycans, Cardiology and Cardiovascular Medicine, MESH: Neovascularization, Physiologic, MESH: Cells, Cultured, MESH : Blood Proteins, MESH : Anoxia, Biological Availability, Neovascularization, Physiologic, MESH : Mice, Inbred C57BL, Angiopoietin-like 4 Protein, In Vitro Techniques, Biology, MESH: Extracellular Matrix, MESH: Actins, Article, MESH: Cell Adhesion, Angiopoietin, 03 medical and health sciences, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, MESH : Ischemia, MESH: Mice, Inbred C57BL, MESH : Mice, MESH : Cells, Cultured, Cell Adhesion, MESH: Cytoskeleton, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, Angiopoietin-Like Protein 4, Animals, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, [ SDV.BBM ] Life Sciences [q-bio]/Biochemistry, Molecular Biology, MESH: Mice, 030304 developmental biology, MESH : Hindlimb, MESH : Endothelial Cells, Heparin, Endothelial Cells, Actin cytoskeleton, Actins, Mice, Inbred C57BL, MESH : Cell Adhesion, MESH : Heparin, MESH : Animals, MESH: Ischemia, Angiopoietins
Abstract

Angiopoietin-like 4 (ANGPTL4) is a secreted protein that belongs to the angiopoietin family and is involved in angiogenesis and metabolism regulation. We previously reported the induction of angptl4 by hypoxia in endothelial cells and in human ischemic tissues from peripheral artery disease. We here observed in a mouse model of hindlimb ischemia that the mRNA upregulation in the vessels correlates with the accumulation of the full-length protein in ischemic tissues. We then investigated its functions in endothelial cells. In response to hypoxia, endogenous ANGPTL4 accumulates in the subendothelial extracellular matrix (ECM). Although the secreted protein undergoes proteolysis leading to truncated fragments present in the medium, only full-length ANGPTL4 interacts with the ECM. Competition and direct binding assays indicate that the strong interaction of ANGPTL4 with the ECM is heparin/heparan sulfate proteoglycan dependent. The balance between matrix-associated and soluble forms of ANGPTL4 points to the role of the ECM in the regulation of its bioavailability. The angiogenic function of the ECM-bound full-length protein was investigated using either the form associated with the conditioned ECM from ANGPTL4-transfected HEK293 cells or the purified immobilized protein. We show that matrix-associated and immobilized ANGPTL4 limit the formation of actin stress fibers and focal contacts in the adhering endothelial cells and inhibit their adhesion. Immobilized ANGPTL4 also decreases motility of endothelial cells and inhibits the sprouting and tube formation. Altogether, these findings show that hypoxic endothelial cells accumulate ANGPTL4 in the ECM, which in turn negatively regulates their angiogenic capacities through an autocrine pathway.

Published
2006
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5. Angiogenin distribution in human term placenta, and expression by cultured trophoblastic cells

Author

Josette Badet, Danièle Evain-Brion, Yann Bassaglia, Jean-Louis Frendo, Elissavet Hatzi, Nadine Pavlov, Développement humain : Croissance et différenciation, Institut des sciences du Médicament -Toxicologie - Chimie - Environnement (IFR71), Institut de Recherche pour le Développement (IRD)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratory of Biological Chemistry, University of Ioannina, Laboratoire de recherche sur la croissance cellulaire, la réparation et la régénération tissulaires (LRCCRRT), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Centre National de la Recherche Scientifique (CNRS), INSERM, Ministère de la Recherche et de la Technologie, Association de la Recherche sur le Cancer, Ligue contre le Cancer, Novo Nordisk Pharmaceutique S.A., Institut National de la Santé et de la Recherche Médicale (INSERM)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Paris Descartes - Paris 5 (UPD5)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Santé et de la Recherche Médicale (INSERM) - Ecole Nationale Supérieure de Chimie de Paris- Chimie ParisTech-PSL (ENSCP) - Centre National de la Recherche Scientifique (CNRS) - Institut de Recherche pour le Développement (IRD) - Université Paris Descartes - Paris 5 (UPD5) - Institut National de la Santé et de la Recherche Médicale (INSERM) - Ecole Nationale Supérieure de Chimie de Paris- Chimie ParisTech-PSL (ENSCP) - Centre National de la Recherche Scientifique (CNRS) - Institut de Recherche pour le Développement (IRD) - Université Paris Descartes - Paris 5 (UPD5) - Université Paris Descartes - Paris 5 (UPD5) - Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12) - Centre National de la Recherche Scientifique (CNRS), and Badet, Josette

Subjects
Cancer Research, Physiology, Angiogenesis, MESH: Trophoblasts, MESH : Immunohistochemistry, Placenta, Clinical Biochemistry, MESH: Ribonuclease, Pancreatic, MESH : Ribonuclease, Pancreatic, Gene Expression, MESH : Pregnancy Trimester, Third, MESH : Tissue Distribution, MESH : Fluorescent Antibody Technique, Indirect, chemistry.chemical_compound, 0302 clinical medicine, MESH: Pregnancy, Pregnancy, MESH: Reverse Transcriptase Polymerase Chain Reaction, MESH : Female, Tissue Distribution, Fluorescent Antibody Technique, Indirect, MESH : Culture Media, Conditioned, Tissue homeostasis, reproductive and urinary physiology, Cells, Cultured, In Situ Hybridization, 0303 health sciences, MESH : Neovascularization, Physiologic, MESH: Culture Media, Conditioned, Reverse Transcriptase Polymerase Chain Reaction, MESH : Reverse Transcriptase Polymerase Chain Reaction, Trophoblast, MESH : In Situ Hybridization, MESH: Enzyme-Linked Immunosorbent Assay, MESH: Placenta, MESH : Enzyme-Linked Immunosorbent Assay, Immunohistochemistry, Trophoblasts, Endothelial stem cell, Vascular endothelial growth factor, medicine.anatomical_structure, MESH : Placenta, Placental ribonuclease inhibitor, 030220 oncology & carcinogenesis, embryonic structures, MESH: Pregnancy Trimester, Third, Female, MESH : Trophoblasts, MESH: Neovascularization, Physiologic, MESH: Cells, Cultured, MESH: Gene Expression, Angiogenin, Pregnancy Trimester, Third, Neovascularization, Physiologic, Enzyme-Linked Immunosorbent Assay, Biology, Article, 03 medical and health sciences, Syncytiotrophoblast, MESH: In Situ Hybridization, MESH : Cells, Cultured, medicine, MESH: Fluorescent Antibody Technique, Indirect, Humans, MESH: Tissue Distribution, [SDV.BDLR] Life Sciences [q-bio]/Reproductive Biology, 030304 developmental biology, MESH: Humans, MESH : Humans, MESH: Biological Markers, MESH: Immunohistochemistry, [SDV.BDLR]Life Sciences [q-bio]/Reproductive Biology, Ribonuclease, Pancreatic, Molecular biology, MESH : Biological Markers, MESH : Gene Expression, MESH : Pregnancy, chemistry, Culture Media, Conditioned, MESH: Female, Biomarkers
Abstract

International audience; Human angiogenin is a 14-kDa secreted protein with angiogenic and ribonucleolytic activities. Angiogenin is associated with tumour development but is also present in normal biological fluids and tissues. To further address the physiological role of angiogenin, we studied its expression in situ and in vitro, using the human term placenta as a model of physiological angiogenesis. Angiogenin was immunodetected by light and transmission electron microscopy, and its cellular distribution was established by double immunolabelling with cell markers including von Willebrand factor, platelet/endothelial cell adhesion molecule-1 (PECAM-1), CD34, Tie-2, vascular endothelial cadherin (VE-cadherin), vascular endothelial growth factor receptor-2 (VEGF-R2), erythropoeitin receptor (Epo-R), alpha-smooth muscle actin, CD45, cytokeratin 7, and Ki-67. Angiogenin immunoreactivity was detected in villous and extravillous trophoblasts, the trophoblast basement membrane, the endothelial basal lamina, foetal blood vessels, foetal and maternal red blood cells, and amnionic cells. Its expression was confirmed by in situ hybridisation with a digoxygenin-labelled cDNA probe and reverse transcriptase-polymerase chain reaction amplification. Villous cytotrophoblasts, isolated and differentiated in vitro into a functional syncytiotrophoblast, expressed and secreted angiogenin. Given its known biological activities in vitro and its observed pattern of expression, these data suggest that, in human placenta, angiogenin has a role not only in angiogenesis but also in vascular and tissue homeostasis, maternal immune tolerance of the foetus, and host defences.

Published
2004
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