SwePub
Sök i LIBRIS databas

  Extended search

WFRF:(Smith Geoffrey)
 

Search: WFRF:(Smith Geoffrey) > (2020-2024) > Immunothrombosis an...

  • Globisch, Maria A.Uppsala universitet,Vaskulärbiologi,Magnusson (author)

Immunothrombosis and vascular heterogeneity in cerebral cavernous malformation

  • Article/chapterEnglish2022

Publisher, publication year, extent ...

  • American Society of Hematology,2022
  • electronicrdacarrier

Numbers

  • LIBRIS-ID:oai:DiVA.org:uu-489038
  • https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-489038URI
  • https://doi.org/10.1182/blood.2021015350DOI
  • https://res.slu.se/id/publ/118492URI

Supplementary language notes

  • Language:English
  • Summary in:Swedish

Part of subdatabase

Classification

  • Subject category:ref swepub-contenttype
  • Subject category:art swepub-publicationtype

Notes

  • Cerebral cavernous malformation (CCM) is a neurovascular disease that results in various neurological symptoms. Thrombi have been reported in surgically resected CCM patient biopsies, but the molecular signatures of these thrombi remain elusive. Here, we investigated the kinetics of thrombi formation in CCM and how thrombi affect the vasculature and contribute to cerebral hypoxia. We used RNA sequencing to investigate the transcriptome of mouse brain endothelial cells with an inducible endothelial-specific Ccm3 knock-out (Ccm3-iECKO). We found that Ccm3-deficient brain endothelial cells had a higher expression of genes related to the coagulation cascade and hypoxia when compared with wild-type brain endothelial cells. Immunofluorescent assays identified key molecular signatures of thrombi such as fibrin, von Willebrand factor, and activated platelets in Ccm3-iECKO mice and human CCM biopsies. Notably, we identified polyhedrocytes in Ccm3-iECKO mice and human CCM biopsies and report it for the first time. We also found that the parenchyma surrounding CCM lesions is hypoxic and that more thrombi correlate with higher levels of hypoxia. We created an in vitro model to study CCM pathology and found that human brain endothelial cells deficient for CCM3 expressed elevated levels of plasminogen activator inhibitor-1 and had a redistribution of von Willebrand factor. With transcriptomics, comprehensive imaging, and an in vitro CCM preclinical model, this study provides experimental evidence that genes and proteins related to the coagulation cascade affect the brain vasculature and promote neurological side effects such as hypoxia in CCMs. This study supports the concept that antithrombotic therapy may be beneficial for patients with CCM.

Subject headings and genre

Added entries (persons, corporate bodies, meetings, titles ...)

  • Onyeogaziri, Favour C.Uppsala universitet,Vaskulärbiologi,Magnusson(Swepub:uu)favon830 (author)
  • Jauhiainen, SuviUppsala universitet,Vaskulärbiologi,Dejana(Swepub:uu)suvja782 (author)
  • Yau, Anthony C. Y.Uppsala universitet,Vaskulärbiologi,Dejana(Swepub:uu)antya284 (author)
  • Orsenigo, FabrizioVascular Biology Unit, IFOM ETS—The AIRC Institute of Molecular Oncology, Milan, Italy (author)
  • Conze, Lei L.Uppsala universitet,Vaskulärbiologi,Dejana(Swepub:uu)leliu102 (author)
  • Arce, MaximilianoUppsala universitet,Vaskulärbiologi,Dejana(Swepub:uu)maxar829 (author)
  • Corada, MonicaVascular Biology Unit, IFOM ETS—The AIRC Institute of Molecular Oncology, Milan, Italy (author)
  • Smith, Ross O.Uppsala universitet,Vaskulärbiologi,Dejana(Swepub:uu)rossm781 (author)
  • Rorsman, CharlotteUppsala universitet,Vaskulärbiologi,Dejana(Swepub:uu)charrors (author)
  • Sundell, VeronicaUppsala universitet,Vaskulärbiologi,Dejana(Swepub:uu)versu224 (author)
  • Fernando, DineshSwedish University of Agricultural Sciences,Sveriges lantbruksuniversitet,Skogens biomaterial och teknologi,Department of Forest Biomaterials and Technology,Department of Biomaterials and Technology/Wood Science, Swedish University of Agricultural Sciences, Uppsala, Sweden(Swepub:slu)50319 (author)
  • Daniel, GeoffreySwedish University of Agricultural Sciences,Sveriges lantbruksuniversitet,Skogens biomaterial och teknologi,Department of Forest Biomaterials and Technology,Department of Biomaterials and Technology/Wood Science, Swedish University of Agricultural Sciences, Uppsala, Sweden(Swepub:slu)47230 (author)
  • Mattsson, OscarUppsala universitet,Vaskulärbiologi,Dejana (author)
  • Savander, HenriDepartment of Neurosurgery, University of Helsinki and Helsinki University Hospital, Helsinki, Finland (author)
  • Wanders, AlkwinDepartment of Clinical Medicine, Aalborg University Hospital, Aalborg, Denmark (author)
  • Rezai Jahromi, BehnamDepartment of Neurosurgery, University of Helsinki and Helsinki University Hospital, Helsinki, Finland (author)
  • Laakso, AkiDepartment of Neurosurgery, University of Helsinki and Helsinki University Hospital, Helsinki, Finland (author)
  • Niemelä, MikaDepartment of Neurosurgery, University of Helsinki and Helsinki University Hospital, Helsinki, Finland (author)
  • Dejana, ElisabettaUppsala universitet,Vaskulärbiologi,Vascular Biology Unit, IFOM ETS—The AIRC Institute of Molecular Oncology, Milan, Italy,Dejana(Swepub:uu)elide443 (author)
  • Magnusson, Peetra U.Uppsala universitet,Vaskulärbiologi,Magnusson(Swepub:uu)petrmagn (author)
  • Uppsala universitetVaskulärbiologi (creator_code:org_t)
  • Sveriges lantbruksuniversitet

Related titles

  • In:Blood: American Society of Hematology140:20, s. 2154-21690006-49711528-0020

Internet link

Find in a library

  • Blood (Search for host publication in LIBRIS)

To the university's database

Kungliga biblioteket hanterar dina personuppgifter i enlighet med EU:s dataskyddsförordning (2018), GDPR. Läs mer om hur det funkar här.
Så här hanterar KB dina uppgifter vid användning av denna tjänst.

 
pil uppåt Close

Copy and save the link in order to return to this view