The presence of circulating human apolipoprotein J reduces the occurrence of cerebral microbleeds in a transgenic mouse model with cerebral amyloid angiopathy
Apolipoprotein J; Cerebral amyloid Angiopathy; Cerebral microbleeds
| Autores: | , , , , , , , , |
|---|---|
| Tipo de recurso: | artículo |
| Estado: | Versión publicada |
| Fecha de publicación: | 2024 |
| País: | España |
| Institución: | Departament de Salut de la Generalitat de Catalunya (DS) |
| Repositorio: | Scientia. Dipòsit d'Informació Digital del Departament de Salut |
| OAI Identifier: | oai:scientiasalut.gencat.cat:11351/12002 |
| Acceso en línea: | https://hdl.handle.net/11351/12002 |
| Access Level: | acceso abierto |
| Palabra clave: | Apolipoproteïnes Hemorràgia cerebral Ratolins transgènics Malalties cerebrovasculars - Tractament ORGANISMS::Eukaryota::Animals::Animal Population Groups::Animals, Genetically Modified::Mice, Transgenic DISEASES::Nervous System Diseases::Central Nervous System Diseases::Brain Diseases::Cerebrovascular Disorders::Intracranial Hemorrhages::Cerebral Hemorrhage DISEASES::Nervous System Diseases::Central Nervous System Diseases::Brain Diseases::Cerebrovascular Disorders::Intracranial Arterial Diseases::Cerebral Arterial Diseases::Cerebral Amyloid Angiopathy Other subheadings::Other subheadings::Other subheadings::/drug therapy CHEMICALS AND DRUGS::Amino Acids, Peptides, and Proteins::Peptides::Amyloid beta-Peptides ORGANISMOS::Eukaryota::animales::grupos de población animal::animales modificados genéticamente::ratones transgénicos ENFERMEDADES::enfermedades del sistema nervioso::enfermedades del sistema nervioso central::enfermedades cerebrales::trastornos cerebrovasculares::hemorragias intracraneales::hemorragia cerebral ENFERMEDADES::enfermedades del sistema nervioso::enfermedades del sistema nervioso central::enfermedades cerebrales::trastornos cerebrovasculares::enfermedades arteriales intracraneales::enfermedades arteriales cerebrales::angiopatía amiloide cerebral Otros calificadores::Otros calificadores::Otros calificadores::/farmacoterapia COMPUESTOS QUÍMICOS Y DROGAS::aminoácidos, péptidos y proteínas::péptidos::péptidos beta amiloides |
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The presence of circulating human apolipoprotein J reduces the occurrence of cerebral microbleeds in a transgenic mouse model with cerebral amyloid angiopathy |
| title |
The presence of circulating human apolipoprotein J reduces the occurrence of cerebral microbleeds in a transgenic mouse model with cerebral amyloid angiopathy |
| spellingShingle |
The presence of circulating human apolipoprotein J reduces the occurrence of cerebral microbleeds in a transgenic mouse model with cerebral amyloid angiopathy Lope-Piedrafita, Silvia Apolipoproteïnes Hemorràgia cerebral Ratolins transgènics Malalties cerebrovasculars - Tractament ORGANISMS::Eukaryota::Animals::Animal Population Groups::Animals, Genetically Modified::Mice, Transgenic DISEASES::Nervous System Diseases::Central Nervous System Diseases::Brain Diseases::Cerebrovascular Disorders::Intracranial Hemorrhages::Cerebral Hemorrhage DISEASES::Nervous System Diseases::Central Nervous System Diseases::Brain Diseases::Cerebrovascular Disorders::Intracranial Arterial Diseases::Cerebral Arterial Diseases::Cerebral Amyloid Angiopathy Other subheadings::Other subheadings::Other subheadings::/drug therapy CHEMICALS AND DRUGS::Amino Acids, Peptides, and Proteins::Peptides::Amyloid beta-Peptides ORGANISMOS::Eukaryota::animales::grupos de población animal::animales modificados genéticamente::ratones transgénicos ENFERMEDADES::enfermedades del sistema nervioso::enfermedades del sistema nervioso central::enfermedades cerebrales::trastornos cerebrovasculares::hemorragias intracraneales::hemorragia cerebral ENFERMEDADES::enfermedades del sistema nervioso::enfermedades del sistema nervioso central::enfermedades cerebrales::trastornos cerebrovasculares::enfermedades arteriales intracraneales::enfermedades arteriales cerebrales::angiopatía amiloide cerebral Otros calificadores::Otros calificadores::Otros calificadores::/farmacoterapia COMPUESTOS QUÍMICOS Y DROGAS::aminoácidos, péptidos y proteínas::péptidos::péptidos beta amiloides |
| title_short |
The presence of circulating human apolipoprotein J reduces the occurrence of cerebral microbleeds in a transgenic mouse model with cerebral amyloid angiopathy |
| title_full |
The presence of circulating human apolipoprotein J reduces the occurrence of cerebral microbleeds in a transgenic mouse model with cerebral amyloid angiopathy |
| title_fullStr |
The presence of circulating human apolipoprotein J reduces the occurrence of cerebral microbleeds in a transgenic mouse model with cerebral amyloid angiopathy |
| title_full_unstemmed |
The presence of circulating human apolipoprotein J reduces the occurrence of cerebral microbleeds in a transgenic mouse model with cerebral amyloid angiopathy |
| title_sort |
The presence of circulating human apolipoprotein J reduces the occurrence of cerebral microbleeds in a transgenic mouse model with cerebral amyloid angiopathy |
| dc.creator.none.fl_str_mv |
Lope-Piedrafita, Silvia Lucas-Parra, Maria Marazuela , Paula Bonaterra Pastra, Anna Solé, Montse Castellote Bellés, Laura Pancorbo, Olalla Rodriguez-Luna, David Hernandez Guillamon, Maria Mar |
| author |
Lope-Piedrafita, Silvia |
| author_facet |
Lope-Piedrafita, Silvia Lucas-Parra, Maria Marazuela , Paula Bonaterra Pastra, Anna Solé, Montse Castellote Bellés, Laura Pancorbo, Olalla Rodriguez-Luna, David Hernandez Guillamon, Maria Mar |
| author_role |
author |
| author2 |
Lucas-Parra, Maria Marazuela , Paula Bonaterra Pastra, Anna Solé, Montse Castellote Bellés, Laura Pancorbo, Olalla Rodriguez-Luna, David Hernandez Guillamon, Maria Mar |
| author2_role |
author author author author author author author author |
| dc.contributor.none.fl_str_mv |
Institut Català de la Salut [Bonaterra-Pastra A, Lucas-Parra M, Marazuela P, Hernández-Guillamon M] Grup de Recerca de Malalties Neurovasculars, Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. Universitat Autònoma de Barcelona, Bellaterra, Spain. [Solé M] Grup de Recerca de Malalties Neurovasculars, Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. Universitat Autònoma de Barcelona, Bellaterra, Spain. Departament of Bioquímica i Biologia Molecular, Institut de Neurociències, Universitat Autònoma de Barcelona, Bellaterra, Spain. [Lope-Piedrafita S] Departament de Ressonància Magnètica Nuclear, Universitat Autònoma de Barcelona, Bellaterra, Spain. [Castellote L] Servei de Bioquímica Clínica, Laboratoris Clínics, Vall d’Hebron Hospital Universitari, Barcelona, Spain. [Pancorbo O, Rodríguez-Luna D] Grup de Recerca en Ictus, Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain Vall d'Hebron Barcelona Hospital Campus |
| dc.subject.none.fl_str_mv |
Apolipoproteïnes Hemorràgia cerebral Ratolins transgènics Malalties cerebrovasculars - Tractament ORGANISMS::Eukaryota::Animals::Animal Population Groups::Animals, Genetically Modified::Mice, Transgenic DISEASES::Nervous System Diseases::Central Nervous System Diseases::Brain Diseases::Cerebrovascular Disorders::Intracranial Hemorrhages::Cerebral Hemorrhage DISEASES::Nervous System Diseases::Central Nervous System Diseases::Brain Diseases::Cerebrovascular Disorders::Intracranial Arterial Diseases::Cerebral Arterial Diseases::Cerebral Amyloid Angiopathy Other subheadings::Other subheadings::Other subheadings::/drug therapy CHEMICALS AND DRUGS::Amino Acids, Peptides, and Proteins::Peptides::Amyloid beta-Peptides ORGANISMOS::Eukaryota::animales::grupos de población animal::animales modificados genéticamente::ratones transgénicos ENFERMEDADES::enfermedades del sistema nervioso::enfermedades del sistema nervioso central::enfermedades cerebrales::trastornos cerebrovasculares::hemorragias intracraneales::hemorragia cerebral ENFERMEDADES::enfermedades del sistema nervioso::enfermedades del sistema nervioso central::enfermedades cerebrales::trastornos cerebrovasculares::enfermedades arteriales intracraneales::enfermedades arteriales cerebrales::angiopatía amiloide cerebral Otros calificadores::Otros calificadores::Otros calificadores::/farmacoterapia COMPUESTOS QUÍMICOS Y DROGAS::aminoácidos, péptidos y proteínas::péptidos::péptidos beta amiloides |
| topic |
Apolipoproteïnes Hemorràgia cerebral Ratolins transgènics Malalties cerebrovasculars - Tractament ORGANISMS::Eukaryota::Animals::Animal Population Groups::Animals, Genetically Modified::Mice, Transgenic DISEASES::Nervous System Diseases::Central Nervous System Diseases::Brain Diseases::Cerebrovascular Disorders::Intracranial Hemorrhages::Cerebral Hemorrhage DISEASES::Nervous System Diseases::Central Nervous System Diseases::Brain Diseases::Cerebrovascular Disorders::Intracranial Arterial Diseases::Cerebral Arterial Diseases::Cerebral Amyloid Angiopathy Other subheadings::Other subheadings::Other subheadings::/drug therapy CHEMICALS AND DRUGS::Amino Acids, Peptides, and Proteins::Peptides::Amyloid beta-Peptides ORGANISMOS::Eukaryota::animales::grupos de población animal::animales modificados genéticamente::ratones transgénicos ENFERMEDADES::enfermedades del sistema nervioso::enfermedades del sistema nervioso central::enfermedades cerebrales::trastornos cerebrovasculares::hemorragias intracraneales::hemorragia cerebral ENFERMEDADES::enfermedades del sistema nervioso::enfermedades del sistema nervioso central::enfermedades cerebrales::trastornos cerebrovasculares::enfermedades arteriales intracraneales::enfermedades arteriales cerebrales::angiopatía amiloide cerebral Otros calificadores::Otros calificadores::Otros calificadores::/farmacoterapia COMPUESTOS QUÍMICOS Y DROGAS::aminoácidos, péptidos y proteínas::péptidos::péptidos beta amiloides |
| description |
Apolipoprotein J; Cerebral amyloid Angiopathy; Cerebral microbleeds |
| publishDate |
2024 |
| dc.date.none.fl_str_mv |
2024 2024 2024 |
| dc.type.none.fl_str_mv |
info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion |
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article |
| status_str |
publishedVersion |
| dc.identifier.none.fl_str_mv |
https://hdl.handle.net/11351/12002 |
| url |
https://hdl.handle.net/11351/12002 |
| dc.language.none.fl_str_mv |
Inglés |
| language_invalid_str_mv |
Inglés |
| dc.relation.none.fl_str_mv |
Alzheimer's Research & Therapy;16 https://doi.org/10.1186/s13195-024-01541-5 info:eu-repo/grantAgreement/ES/PE2017-2020/PI17%2F00275 info:eu-repo/grantAgreement/ES/PE2017-2020/PI20%2F00465 info:eu-repo/grantAgreement/ES/PEICTI2021-2023/PI23%2F00082 info:eu-repo/grantAgreement/ES/PEICTI2021-2023/RD21%2F0006%2F0007 |
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Attribution 4.0 International http://creativecommons.org/licenses/by/4.0/ info:eu-repo/semantics/openAccess |
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Attribution 4.0 International http://creativecommons.org/licenses/by/4.0/ |
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openAccess |
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application/pdf |
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BMC |
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BMC |
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Scientia reponame:Scientia. Dipòsit d'Informació Digital del Departament de Salut instname:Departament de Salut de la Generalitat de Catalunya (DS) |
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Departament de Salut de la Generalitat de Catalunya (DS) |
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Scientia. Dipòsit d'Informació Digital del Departament de Salut |
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Scientia. Dipòsit d'Informació Digital del Departament de Salut |
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1869417477883035648 |
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The presence of circulating human apolipoprotein J reduces the occurrence of cerebral microbleeds in a transgenic mouse model with cerebral amyloid angiopathyLope-Piedrafita, SilviaLucas-Parra, MariaMarazuela , PaulaBonaterra Pastra, AnnaSolé, MontseCastellote Bellés, LauraPancorbo, OlallaRodriguez-Luna, DavidHernandez Guillamon, Maria MarApolipoproteïnesHemorràgia cerebralRatolins transgènicsMalalties cerebrovasculars - TractamentORGANISMS::Eukaryota::Animals::Animal Population Groups::Animals, Genetically Modified::Mice, TransgenicDISEASES::Nervous System Diseases::Central Nervous System Diseases::Brain Diseases::Cerebrovascular Disorders::Intracranial Hemorrhages::Cerebral HemorrhageDISEASES::Nervous System Diseases::Central Nervous System Diseases::Brain Diseases::Cerebrovascular Disorders::Intracranial Arterial Diseases::Cerebral Arterial Diseases::Cerebral Amyloid AngiopathyOther subheadings::Other subheadings::Other subheadings::/drug therapyCHEMICALS AND DRUGS::Amino Acids, Peptides, and Proteins::Peptides::Amyloid beta-PeptidesORGANISMOS::Eukaryota::animales::grupos de población animal::animales modificados genéticamente::ratones transgénicosENFERMEDADES::enfermedades del sistema nervioso::enfermedades del sistema nervioso central::enfermedades cerebrales::trastornos cerebrovasculares::hemorragias intracraneales::hemorragia cerebralENFERMEDADES::enfermedades del sistema nervioso::enfermedades del sistema nervioso central::enfermedades cerebrales::trastornos cerebrovasculares::enfermedades arteriales intracraneales::enfermedades arteriales cerebrales::angiopatía amiloide cerebralOtros calificadores::Otros calificadores::Otros calificadores::/farmacoterapiaCOMPUESTOS QUÍMICOS Y DROGAS::aminoácidos, péptidos y proteínas::péptidos::péptidos beta amiloidesApolipoprotein J; Cerebral amyloid Angiopathy; Cerebral microbleedsApolipoproteína J; Angiopatía amiloide cerebral; Microhemorragias cerebralesApolipoproteïna J; Angiopatia amiloide cerebral; Microhemorràgies cerebralsBackground Cerebral amyloid angiopathy (CAA) is characterized by amyloid-β (Aβ) deposition in cerebral vessels, leading to lobar cerebral microbleeds (CMB) and intracerebral hemorrhages (ICH). Apolipoprotein J (ApoJ) is a multifunctional chaperone related to Aβ aggregation and clearance. Our study investigated the vascular impact of chronic recombinant human Apolipoprotein J (rhApoJ) treatment in a transgenic mouse model of β-amyloidosis with prominent CAA. Methods Twenty-month-old APP23 C57BL/6 mice received 25 doses of rhApoJ (1 mg/kg) (n = 9) or saline (n = 8) intraperitoneally for 13 weeks, while Wild-type (WT) mice received saline (n = 13). Postmortem brains underwent T2*-weighted magnetic resonance imaging (MRI) to detect hemorrhagic lesions. Aβ levels and distribution, cerebral fibrinogen leakage, brain smooth muscle actin (sma), and plasma matrix metalloproteinases and inflammatory markers were analyzed after treatments. Additionally, plasma samples from 22 patients with lobar ICH were examined to determine the clinical relevance of the preclinical findings. Results rhApoJ-treated APP23 presented fewer cortical CMBs (50–300 μm diameter) (p = 0.012) and cortical larger hemorrhages (> 300 μm) (p = 0.002) than saline-treated mice, independently of Aβ brain levels. MRI-detected hemorrhagic lesions correlated with fibrinogen cerebral extravasation (p = 0.011). Additionally, rhApoJ-treated mice presented higher number of sma-positive vessels than saline-treated mice (p = 0.038). In rhApoJ-treated mice, human ApoJ was detected in plasma and in occasional leptomeningeal vessels, but not in the parenchyma, suggesting that its mechanism of action operates through the periphery. The administration of rhApoJ induced an increase in plasma Groα (p = 0.035) and MIP-1α (p = 0.035) levels, while lower MMP-12 (p = 0.046) levels, compared to the saline-treated group. In acute lobar ICH patients, MMP-12 plasma levels correlated with larger hemorrhage volume (p = 0.040) and irregular ICH shape (p = 0.036). Conclusions Chronic rhApoJ treatment in aged APP23 mice ameliorated CAA-related neurovascular damage by reducing the occurrence of CMB. We propose that rhApoJ may prevent blood-brain barrier (BBB) leakage and CMB appearance partly through circulating MMP-12 modulation.This work was funded by the Instituto de Salud Carlos III (ISCIII), (PI17/00275, PI20/00465, PI23/00082) and co-financed by the European Regional Development Fund (FEDER). The Neurovascular Research Laboratory is part of the RICORS‐ICTUS‐Enfermedades Vasculares Cerebrales network funded by Instituto de Salud Carlos III (ISCIII) -RD21/0006/0007) with NextGeneration-European Union Funds. AGAUR supports the Neurovascular Research Laboratory (SGR2021/0656).BMCInstitut Català de la Salut[Bonaterra-Pastra A, Lucas-Parra M, Marazuela P, Hernández-Guillamon M] Grup de Recerca de Malalties Neurovasculars, Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. Universitat Autònoma de Barcelona, Bellaterra, Spain. [Solé M] Grup de Recerca de Malalties Neurovasculars, Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. Universitat Autònoma de Barcelona, Bellaterra, Spain. Departament of Bioquímica i Biologia Molecular, Institut de Neurociències, Universitat Autònoma de Barcelona, Bellaterra, Spain. [Lope-Piedrafita S] Departament de Ressonància Magnètica Nuclear, Universitat Autònoma de Barcelona, Bellaterra, Spain. [Castellote L] Servei de Bioquímica Clínica, Laboratoris Clínics, Vall d’Hebron Hospital Universitari, Barcelona, Spain. [Pancorbo O, Rodríguez-Luna D] Grup de Recerca en Ictus, Vall d’Hebron Institut de Recerca (VHIR), Barcelona, SpainVall d'Hebron Barcelona Hospital Campus202420242024info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfhttps://hdl.handle.net/11351/12002Scientiareponame:Scientia. Dipòsit d'Informació Digital del Departament de Salutinstname:Departament de Salut de la Generalitat de Catalunya (DS)InglésAlzheimer's Research & Therapy;16https://doi.org/10.1186/s13195-024-01541-5info:eu-repo/grantAgreement/ES/PE2017-2020/PI17%2F00275info:eu-repo/grantAgreement/ES/PE2017-2020/PI20%2F00465info:eu-repo/grantAgreement/ES/PEICTI2021-2023/PI23%2F00082info:eu-repo/grantAgreement/ES/PEICTI2021-2023/RD21%2F0006%2F0007Attribution 4.0 Internationalhttp://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:scientiasalut.gencat.cat:11351/120022026-06-12T09:38:37Z |
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15,81155 |