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Circulating biomarkers in familial cerebral cavernous malformation

Lazzaroni, Francesca (författare)
IFOM ETS The AIRC Inst Mol Oncol, Vasc Biol Unit, Milan, Italy.;Fdn IRCCS Ca Granda Osped Maggiore Policlin, Dept Hematol, Via Francesco Sforza 35, I-20122 Milan, Italy.
Meessen, Jennifer M. T. A. (författare)
Inst Pharmacol Res Mario Negri IRCCS, Dept Acute Brain & Cardiovasc Injury, Milan, Italy.
Sun, Ying (författare)
Uppsala universitet,Vaskulärbiologi
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Lanfranconi, Silvia (författare)
Fdn IRCCS Ca Granda Osped Maggiore Policlin, Dept Neurol, Milan, Italy.
Scola, Elisa (författare)
Fdn IRCCS Ca Granda Osped Maggiore Policlin, Dept Neurol, Milan, Italy.;Fdn IRCCS Ca Granda Osped Maggiore Policlin, Dept Neuroradiol, Milan, Italy.
D'Alessandris, Quintino Giorgio (författare)
Fdn Policlin Univ Agostino Gemelli IRCCS, Dept Neurosurg, Rome, Italy.;Univ Cattolica Sacro Cuore, Dept Neurosci, Rome, Italy.
Tassi, Laura (författare)
ASST Niguarda Hosp, Claudio Munari Epilepsy Surg Ctr, Milan, Italy.
Carriero, Maria Rita (författare)
Fdn IRCCS Ist Neurol Carlo Besta, Cerebrovasc Dis Unit, Milan, Italy.
Castori, Marco (författare)
Fdn IRCCS Casa Sollievo Sofferenza, Div Med Genet, San Giovanni Rotondo, Italy.
Marino, Silvia (författare)
IRCCS Ctr Neurolesi Bonino Pulejo, Messina, Italy.
Blanda, Adriana (författare)
Inst Pharmacol Res Mario Negri IRCCS, Dept Acute Brain & Cardiovasc Injury, Milan, Italy.
Nicolis, Enrico B. (författare)
Inst Pharmacol Res Mario Negri IRCCS, Dept Acute Brain & Cardiovasc Injury, Milan, Italy.
Novelli, Deborah (författare)
Inst Pharmacol Res Mario Negri IRCCS, Dept Acute Brain & Cardiovasc Injury, Milan, Italy.
Calabrese, Roberta (författare)
Inst Pharmacol Res Mario Negri IRCCS, Dept Acute Brain & Cardiovasc Injury, Milan, Italy.
Agnelli, Nicolo M. (författare)
Inst Pharmacol Res Mario Negri IRCCS, Dept Acute Brain & Cardiovasc Injury, Milan, Italy.
Bottazzi, Barbara (författare)
IRCCS Humanitas Res Hosp, Rozzano, Italy.
Leone, Roberto (författare)
IRCCS Humanitas Res Hosp, Rozzano, Italy.
Mazzola, Selene (författare)
Univ Milano Bicocca, Desio Hosp, Lab Med, Milan, Italy.
Besana, Silvia (författare)
Univ Milano Bicocca, Desio Hosp, Lab Med, Milan, Italy.
Catozzi, Carlotta (författare)
Ist Europeo Oncol IRCCS, Dept Expt Oncol, Milan, Italy.
Nezi, Luigi (författare)
Ist Europeo Oncol IRCCS, Dept Expt Oncol, Milan, Italy.
Lampugnani, Maria G. (författare)
IFOM ETS The AIRC Inst Mol Oncol, Vasc Biol Unit, Milan, Italy.;Inst Pharmacol Res Mario Negri IRCCS, Dept Acute Brain & Cardiovasc Injury, Milan, Italy.
Malinverno, Matteo (författare)
IFOM ETS The AIRC Inst Mol Oncol, Vasc Biol Unit, Milan, Italy.
Grdseloff, Nastasja (författare)
Univ Potsdam, Dept Zoophysiol, Inst Biochem & Biol, Potsdam, Germany.
Roedel, Claudia J. (författare)
Univ Potsdam, Dept Zoophysiol, Inst Biochem & Biol, Potsdam, Germany.
Jahromi, Behnam Rezai (författare)
Helsinki Univ Hosp, Dept Neurosurg, Helsinki, Finland.
Bolli, Niccolo (författare)
Fdn IRCCS Ca Granda Osped Maggiore Policlin, Dept Hematol, Milan, Italy.;Univ Milan, Dept Oncol & Hematooncol, Milan, Italy.
Passamonti, Francesco (författare)
Fdn IRCCS Ca Granda Osped Maggiore Policlin, Dept Hematol, Milan, Italy.;Univ Milan, Dept Oncol & Hematooncol, Milan, Italy.
Magnusson, Peetra (författare)
Uppsala universitet,Vaskulärbiologi
Abdelilah-Seyfried, Salim (författare)
Univ Potsdam, Dept Zoophysiol, Inst Biochem & Biol, Potsdam, Germany.
Dejana, Elisabetta (författare)
Uppsala universitet,Vaskulärbiologi,IFOM ETS The AIRC Inst Mol Oncol, Vasc Biol Unit, Milan, Italy.
Latini, Roberto (författare)
Inst Pharmacol Res Mario Negri IRCCS, Dept Acute Brain & Cardiovasc Injury, Milan, Italy.
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IFOM ETS The AIRC Inst Mol Oncol, Vasc Biol Unit, Milan, Italy;Fdn IRCCS Ca Granda Osped Maggiore Policlin, Dept Hematol, Via Francesco Sforza 35, I-20122 Milan, Italy. Inst Pharmacol Res Mario Negri IRCCS, Dept Acute Brain & Cardiovasc Injury, Milan, Italy. (creator_code:org_t)
Elsevier, 2024
2024
Engelska.
Ingår i: EBioMedicine. - : Elsevier. - 2352-3964. ; 99
Relaterad länk:
https://doi.org/10.1...
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https://uu.diva-port... (primary) (Raw object)
https://urn.kb.se/re...
https://doi.org/10.1...
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  • Tidskriftsartikel (refereegranskat)
Abstract Ämnesord
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  • Background Cerebral Cavernous Malformation (CCM) is a rare cerebrovascular disease, characterized by the presence of multiple vascular malformations that may result in intracerebral hemorrhages (ICHs), seizure(s), or focal neurological deficits (FND). Familial CCM (fCCM) is due to loss of function mutations in one of the three independent genes KRIT1 (CCM1), Malcavernin (CCM2), or Programmed Cell death 10 (PDCD10/CCM3). The aim of this study was to identify plasma protein biomarkers of fCCM to assess the severity of the disease and predict its progression.Methods Here, we have investigated plasma samples derived from n = 71 symptomatic fCCM patients (40 female/31 male) and n =17 healthy donors (HD) (9 female/8 male) of the Phase 1/2 Treat_CCM trial, using multiplexed protein profiling approaches.Findings Biomarkers as sCD14 (p = 0.00409), LBP (p = 0.02911), CXCL4 (p = 0.038), ICAM-1 (p = 0.02013), ANG2 (p = 0.026), CCL5 (p = 0.00403), THBS1 (p = 0.0043), CRP (p = 0.0092), and HDL (p = 0.027), were significantly different in fCCM compared to HDs. Of note, sENG (p = 0.011), THBS1 (p = 0.011) and CXCL4 (p = 0.011), were correlated to CCM genotype. sROBO4 (p = 0.014), TM (p = 0.026) and CRP (p = 0.040) were able to predict incident adverse clinical events, such as ICH, FND or seizure. GDF-15, FLT3L, CXCL9, FGF-21 and CDCP1, were identified as predictors of the formation of new MRI-detectable lesions over 2-year follow-up. Furthermore, the functional relevance of ang2, thbs1, robo4 and cdcp1 markers was validated by zebrafish pre-clinical model of fCCM.Interpretation Overall, our study identifies a set of biochemical parameters to predict CCM progression, suggesting biological interpretations and potential therapeutic approaches to CCM disease.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Neurologi (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Neurology (hsv//eng)

Nyckelord

Familial cerebral cavernous malformation
Vascular biology
Biomarkers
Proteomics

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