Non-productive angiogenesis disassembles Aß plaque-associated blood vessels
| Autor: | José Luis Trillo-Contreras, Pedro Gómez-Gálvez, Luis M. Escudero, Nieves Lara-Ureña, Andrea S. Bullones-Bolanos, Javier Vitorica, Miriam Echevarría, Rosana March-Díaz, Miguel Marchena, Jose Carlos Davila, Ana C. Sanchez-Hidalgo, Eloisa Herrera, Fernando de Castro, Jakob Körbelin, Antonia Gutierrez, Rocio González-Martínez, Alicia E. Rosales-Nieves, Raquel del Toro, Clara Ortega-de San Luis, Maria I. Alvarez-Vergara, Alberto Pascual, Pablo Vicente-Munuera, Manuel A. Sanchez-Garcia, Guiomar Rodriguez-Perinan, Martin Trepel, Francisco G. Scholl, Alberto Rábano, Javier Villadiego, Miguel Martin-Bornez, Beatriz Fernández-Gómez |
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| Přispěvatelé: | Universidad de Sevilla. Departamento de Biología Celular, Instituto de Salud Carlos III PI18/01556, PI18/01557, Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas CB06/05/ 0094, Ministerio de Economía, Industria y Competitividad (España), Ministerio de Economía y Competitividad (España), Ministerio de Educación, Cultura y Deporte (España), Instituto de Salud Carlos III, European Commission, Agencia Estatal de Investigación (España), Ministerio de Ciencia, Innovación y Universidades (España), Fundació La Marató de TV3, Junta de Andalucía, Fundación Domingo Martínez, [Alvarez-Vergara,MI, Rosales-Nieves,AE, March-Diaz,R, Rodriguez-Perinan,G, Lara-Ureña,N, Ortega-de San Luis,C, Sanchez-Garcia,MA, Martin-Bornez,M, Gómez-Gálvez,P, Vicente-Munuera,P, Bullones-Bolanos,AS, Trillo-Contreras,JL, Sanchez-Hidalgo,AC, del Toro,R, Scholl,FG, Escudero,LM, Villadiego,J, Echevarria,M, Vitorica,J, Pascual,A] Instituto de Biomedicina de Sevilla (IBiS), Hospital Universitario Virgen del Rocio/CSIC/Universidad de Sevilla, Seville, Spain. [Gómez-Gálvez,P, Escudero,LM] Department of Biología Celular, Universidad de Sevilla. Seville, Spain. [Gómez-Gálvez,P, Davila,JC, Gutierrez,A, Vitorica,J] Centro de Investigacion Biomedica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Madrid, Spain. [Fernandez-Gomez,B, Marchena,MA, de Castro,F] Grupo de Neurobiología del Desarrollo-GNDe, Instituto Cajal-CSIC, Madrid, Spain. [Marchena,MA] Departamento de Medicina, Facultad de Ciencias, Biomédicas y de la Salud, Universidad Europea de Madrid, Villaviciosa de Odón, Spain. [Davila,JC, Gutierrez,A] Department of Biologia Celular, Genetica y Fisiologia, Facultad de Ciencias, Instituto de Investigacion Biomedica de Malaga (IBIMA), Universidad de Malaga, Malaga, Spain. [Gonzalez-Martinez,R, Herrera,E] 7 Instituto de Neurociencias de Alicante, Consejo Superior de Investigaciones Científicas-Universidad Miguel Hernández (CSIC-UMH), Alicante, Spain. [Trillo-Contreras,JL, Echevarria,M] Department of Fisiología Médica y Biofisica, Universidad de Sevilla, Seville, Spain. [del Toro,R] Centro de Investigacion Biomedica en Red de Enfermedades Cardiovasculares (CIBER-CV), Madrid, Spain. [Trepel,M] Augsburg Medical Center, Department of Hematology and Oncology, Augsburg, Germany. [Körbelin,J] Section of Pneumology, Department of Oncology, Hematology and Stem Cell Transplantation, University Medical Center Hamburg-Eppendorf, Hamburg, Germany. [Rabano,A] Fundacion CIEN, Madrid, Spain. [Vitorica,J] Department of Bioquimica y Biologia Molecular, Facultad de Farmacia, Universidad de Sevilla, Seville, Spain. [Ortega-de San Luis,L] Present address: School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College of Dublin, Dublin, Ireland. [Sanchez-Garcia,MA] Present address: Centre for Inflammation Research, Queen’s Medical Research Institute, University of Edinburgh, Edinburgh, UK. [Alvarez-Vergara,MI, Rosales-Nieves,AE] These authors contributed equally: Maria I. Alvarez-Vergara, Alicia E. Rosales-Nieves., A.E.R.-N. was the recipient of a JdlC-F fellowship from the Spanish Ministry of Economy, Industry, and Competitiveness (MINEICO) (FJCI-2015-23708), M.I.A.-V., N.L.-U., and C.O.-d.S.L. were the recipient of an FPU fellowship from Spanish Ministry of Education, Culture, and Sport (respectively, FPU15/02898, FPU14-02115, and AP2010‐1598), and R.M.-D. was the recipient of a 'Sara Borrell' fellowship from ISCIII (CD09/0007). Work was supported by grants to A.P. by the Spanish MINEICO, ISCIII, and FEDER (SAF2012‐33816, SAF2015‐64111‐R, RTI2018-096629-B-100, SAF2017-90794-REDT, and PIE13/0004), by the regional Government of Andalusia ('Proyectos de Excelencia', P12‐CTS‐2138 and P12‐CTS‐2232) co-funded by CEC and FEDER funds, and by the 'Ayuda de Biomedicina 2018', Fundación Domingo Martínez, J.Vitorica: Instituto de Salud Carlos III (ISCiii) of Spain, co-financed by FEDER funds from European Union (PI18/01556) by La Marató-TV3 Foundation grant 20141431, by CIBERNED (CB06/05/0094), and by Junta de Andalucia Consejería de Economía y Conocimiento through grant US-1262734, A.G.: Instituto de Salud Carlos III (ISCiii) of Spain, co-financed by FEDER funds from European Union, through grant PI18/01557, and by Junta de Andalucia Consejería de Economía y Conocimiento through grants UMA18-FEDERJA-211 and P18-RT-2233 co-financed by Programa Operativo FEDER 2014-2020. The authors thank Maria Llorens-Martin (CBM-Severo Ochoa, Madrid, Spain) for the generous gift of the human samples, Ralf H. Adams and Jose L. de la Pompa for providing the Cdh5-Cre, Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas |
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Rodentia::Muridae::Murinae::Mice::Mice Inbred Strains::Mice Inbred C57BL [Medical Subject Headings] Cerebrovascular disorders Angiogenesis Malformaciones vasculares Endothelial cells General Physics and Astronomy Plaque Amyloid Molecular neuroscience Neovascularization Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings] 0302 clinical medicine Blood vessels Péptidos beta-amiloides Enfermedad de Alzheimer Organisms::Eukaryota::Animals [Medical Subject Headings] Anatomy::Cells::Epithelial Cells::Endothelial Cells [Medical Subject Headings] Diseases::Pathological Conditions Signs and Symptoms::Pathologic Processes::Metaplasia::Neovascularization Pathologic [Medical Subject Headings] Mice Knockout Chemicals and Drugs::Amino Acids Peptides and Proteins::Proteins::Membrane Proteins::Presenilins [Medical Subject Headings] Multidisciplinary Microglia Neovascularization Pathologic Reverse Transcriptase Polymerase Chain Reaction Placa amiloide Presenilins Brain Alzheimer's disease Cell biology Analytical Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Genetic Techniques::Nucleic Acid Amplification Techniques::Polymerase Chain Reaction::Reverse Transcriptase Polymerase Chain Reaction [Medical Subject Headings] medicine.anatomical_structure Vasos sanguíneos Anatomy::Cardiovascular System::Blood Vessels::Microvessels [Medical Subject Headings] Encéfalo Female medicine.symptom Alzheimer disease Blood vessel Diseases::Nervous System Diseases::Neurodegenerative Diseases::Tauopathies::Alzheimer Disease [Medical Subject Headings] Phagocytosis Science Vascular malformations Presenilinas Diseases::Skin and Connective Tissue Diseases::Skin Diseases::Skin Abnormalities [Medical Subject Headings] Mice Transgenic Analytical Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Genetic Techniques::Gene Expression Profiling [Medical Subject Headings] Biology General Biochemistry Genetics and Molecular Biology Presenilin Article Plaque amyloid 03 medical and health sciences Alzheimer Disease Diseases::Pathological Conditions Signs and Symptoms::Pathological Conditions Anatomical::Plaque Amyloid [Medical Subject Headings] medicine Extracellular Animals Humans ddc:610 Anatomy::Cardiovascular System::Blood Vessels [Medical Subject Headings] Amyloid beta-Peptides Gene Expression Profiling Células endoteliales Endothelial Cells General Chemistry Chemicals and Drugs::Amino Acids Peptides and Proteins::Peptides::Amyloid beta-Peptides [Medical Subject Headings] Anatomy::Nervous System::Central Nervous System::Brain [Medical Subject Headings] Diseases::Animal Diseases::Disease Models Animal [Medical Subject Headings] Mice Inbred C57BL Disease Models Animal 030104 developmental biology Check Tags::Female [Medical Subject Headings] Blood Vessels Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Rodentia::Muridae::Murinae::Mice::Mice Transgenic [Medical Subject Headings] 030217 neurology & neurosurgery Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Rodentia::Muridae::Murinae::Mice::Mice Mutant Strains::Mice Knockout [Medical Subject Headings] |
| Zdroj: | idUS: Depósito de Investigación de la Universidad de Sevilla Universidad de Sevilla (US) Nature Communications Digital.CSIC. Repositorio Institucional del CSIC instname Nature Communications, Vol 12, Iss 1, Pp 1-16 (2021) idUS. Depósito de Investigación de la Universidad de Sevilla |
| Popis: | The human Alzheimer’s disease (AD) brain accumulates angiogenic markers but paradoxically, the cerebral microvasculature is reduced around Aß plaques. Here we demonstrate that angiogenesis is started near Aß plaques in both AD mouse models and human AD samples. However, endothelial cells express the molecular signature of non-productive angiogenesis (NPA) and accumulate, around Aß plaques, a tip cell marker and IB4 reactive vascular anomalies with reduced NOTCH activity. Notably, NPA induction by endothelial loss of presenilin, whose mutations cause familial AD and which activity has been shown to decrease with age, produced a similar vascular phenotype in the absence of Aß pathology. We also show that Aß plaque-associated NPA locally disassembles blood vessels, leaving behind vascular scars, and that microglial phagocytosis contributes to the local loss of endothelial cells. These results define the role of NPA and microglia in local blood vessel disassembly and highlight the vascular component of presenilin loss of function in AD. A.E.R.-N. was the recipient of a JdlC-F fellowship from the Spanish Ministry of Economy, Industry, and Competitiveness (MINEICO) (FJCI-2015-23708), M.I.A.-V., N.L.-U., and C.O.-d.S.L. were the recipient of an FPU fellowship from Spanish Ministry of Education, Culture, and Sport (respectively, FPU15/02898, FPU14-02115, and AP2010‐1598), and R.M.-D. was the recipient of a “Sara Borrell” fellowship from ISCIII (CD09/0007). Work was supported by grants to A.P. by the Spanish MINEICO, ISCIII, and FEDER (SAF2012‐33816, SAF2015‐64111‐R, RTI2018-096629-B-100, SAF2017-90794-REDT, and PIE13/0004), by the regional Government of Andalusia (“Proyectos de Excelencia”, P12‐CTS‐2138 and P12‐CTS‐2232) co-funded by CEC and FEDER funds, and by the “Ayuda de Biomedicina 2018”, Fundación Domingo Martínez; J.Vitorica: Instituto de Salud Carlos III (ISCiii) of Spain, co-financed by FEDER funds from European Union (PI18/01556) by La Marató-TV3 Foundation grant 20141431; by CIBERNED (CB06/05/0094); and by Junta de Andalucia Consejería de Economía y Conocimiento through grant US-1262734; A.G.: Instituto de Salud Carlos III (ISCiii) of Spain, co-financed by FEDER funds from European Union, through grant PI18/01557; and by Junta de Andalucia Consejería de Economía y Conocimiento through grants UMA18-FEDERJA-211 and P18-RT-2233 co-financed by Programa Operativo FEDER 2014-2020. |
| Databáze: | OpenAIRE |
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