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Proteomics on human...
Proteomics on human cerebral cavernous malformations reveals novel biomarkers in neurovascular dysfunction for the disease pathology
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- Jauhiainen, Suvi (author)
- Uppsala universitet,Vaskulärbiologi,Univ Eastern Finland, AI Virtanen Inst Mol Sci, Kuopio, Finland.
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- Onyeogaziri, Favour C. (author)
- Uppsala universitet,Vaskulärbiologi
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- Lazzaroni, Francesca (author)
- Fdn IRCCS Ca Granda Osped Maggiore Policlin, Hematol Unit, Milan, Italy.
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- Liu Conze, Lei (author)
- Uppsala universitet,Vaskulärbiologi
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- Laakkonen, Johanna P. (author)
- Univ Eastern Finland, AI Virtanen Inst Mol Sci, Kuopio, Finland.
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- Laham-Karam, Nihay (author)
- Univ Eastern Finland, AI Virtanen Inst Mol Sci, Kuopio, Finland.
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- Laakso, Aki (author)
- Univ Helsinki, Dept Neurosurg, Helsinki, Finland.;Helsinki Univ Hosp, Helsinki, Finland.
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- Niemela, Mika (author)
- Univ Helsinki, Dept Neurosurg, Helsinki, Finland.;Helsinki Univ Hosp, Helsinki, Finland.
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- Jahromi, Behnam Rezai (author)
- Univ Helsinki, Dept Neurosurg, Helsinki, Finland.;Helsinki Univ Hosp, Helsinki, Finland.
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- Magnusson, Peetra U. (author)
- Uppsala universitet,Vaskulärbiologi
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(creator_code:org_t)
- Elsevier, 2024
- 2024
- English.
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In: Biochimica et Biophysica Acta - Molecular Basis of Disease. - : Elsevier. - 0925-4439 .- 1879-260X. ; 1870:5
- Related links:
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
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- Background: Cerebral cavernous malformation (CCM) is a disease associated with an elevated risk of focal neurological deficits, seizures, and hemorrhagic stroke. The disease has an inflammatory profile and improved knowledge of CCM pathology mechanisms and exploration of candidate biomarkers will enable new non-invasive treatments. Methods: We analyzed protein signatures in human CCM tissue samples by using a highly specific and sensitive multiplexing technique, proximity extension assay. Findings: Data analysis revealed CCM specific proteins involved in endothelial dysfunction/inflammation/activation, leukocyte infiltration/chemotaxis, hemostasis, extracellular matrix dysfunction, astrocyte and microglial cell activation. Biomarker expression profiles matched bleeding status, especially with higher levels of inflammatory markers and activated astrocytes in ruptured than non-ruptured samples, some of these biomarkers are secreted into blood or urine. Furthermore, analysis was also done in a spatially resolving manner by separating the lesion area from the surrounding brain tissue. Our spatial studies revealed that although appearing histologically normal, the CCM border areas were pathological when compared to control brain tissues. Moreover, the functional relevance of CD93, ICAM-1 and MMP9, markers related to endothelial cell activation and extracellular matrix was validated by a murine pre-clinical CCM model. Interpretation: Here we present a novel strategy for proteomics analysis on human CCMs, offering a possibility for high-throughput protein screening acquiring data on the local environment in the brain. Our data presented here describe CCM relevant brain proteins and specifically those which are secreted can serve the need of circulating CCM biomarkers to predict cavernoma's risk of bleeding.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Neurologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Neurology (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Hematologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Hematology (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Neurovetenskaper (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Neurosciences (hsv//eng)
Keyword
- Cerebral cavernous malformation
- CCM
- Biomarkers
- Multiplexing
- Proteomics
- Proximity extension assay
Publication and Content Type
- ref (subject category)
- art (subject category)
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Jauhiainen, Suvi
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Onyeogaziri, Fav ...
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Lazzaroni, Franc ...
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Liu Conze, Lei
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Laakkonen, Johan ...
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Laham-Karam, Nih ...
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Laakso, Aki
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Niemela, Mika
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Jahromi, Behnam ...
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Magnusson, Peetr ...
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and Neurology
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and Hematology
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MEDICAL AND HEAL ...
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