Endothelial Cells Lining Sporadic Cerebral Cavernous Malformation Cavernomas Undergo Endothelial-to-Mesenchymal Transition

Roberto Pallini, Maurizio Martini, Luigi Maria Larocca, Luca Bravi, Matteo Malinverno, Federica Pisati, Noemi Rudini, Roberto Cuttano, Marco Locatelli, Vincenzo Levi, Giulio Andrea Bertani, Elisabetta Dejana, Maria Grazia Lampugnani

Risultato della ricerca: Contributo in rivistaArticolo in rivista

37 Citazioni (Scopus)

Abstract

Background and Purpose-Cerebral cavernous malformation (CCM) is characterized by multiple lumen vascular malformations in the central nervous system that can cause neurological symptoms and brain hemorrhages. About 20% of CCM patients have an inherited form of the disease with ubiquitous loss-of-function mutation in any one of 3 genes CCM1, CCM2, and CCM3. The rest of patients develop sporadic vascular lesions histologically similar to those of the inherited form and likely mediated by a biallelic acquired mutation of CCM genes in the brain vasculature. However, the molecular phenotypic features of endothelial cells in CCM lesions in sporadic patients are still poorly described. This information is crucial for a targeted therapy. Methods-We used immunofluorescence microscopy and immunohistochemistry to analyze the expression of endothelial-to-mesenchymal transition markers in the cavernoma of sporadic CCM patients in parallel with human familial cavernoma as a reference control. Results-We report here that endothelial cells, a cell type critically involved in CCM development, undergo endothelial-to-mesenchymal transition in the lesions of sporadic patients. This switch in endothelial phenotype has been described only in genetic CCM patients and in murine models of the disease. In addition, TGF-β/p-Smad-and β-catenin-dependent signaling pathways seem activated in sporadic cavernomas as in familial ones. Conclusions-Our findings support the use of common therapeutic strategies for both sporadic and genetic CCM malformations.
Lingua originaleEnglish
pagine (da-a)886-890
Numero di pagine5
RivistaStroke
Volume47
DOI
Stato di pubblicazionePubblicato - 2016

Keywords

  • Adolescent
  • Adult
  • Advanced and Specialized Nursing
  • Aged
  • CCM
  • Cardiology and Cardiovascular Medicine
  • Central Nervous System Neoplasms
  • Child
  • EndMT
  • Endothelium, Vascular
  • Epithelial-Mesenchymal Transition
  • Female
  • Hemangioma, Cavernous, Central Nervous System
  • Humans
  • Male
  • Middle Aged
  • Neurology (clinical)
  • Young Adult
  • endothelium
  • immunohistochemistry
  • intracranial hemorrhage

Fingerprint Entra nei temi di ricerca di 'Endothelial Cells Lining Sporadic Cerebral Cavernous Malformation Cavernomas Undergo Endothelial-to-Mesenchymal Transition'. Insieme formano una fingerprint unica.

Cita questo