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Endothelial cell disease: emerging knowledge from cerebral cavernous malformations
- Source :
- Current opinion in hematology. 24(3)
- Publication Year :
- 2017
-
Abstract
- Purpose of review Endothelial cells dysfunctions are crucial determinants of several human diseases. We review here the most recent reports on endothelial cell defects in cerebral cavernous malformations (CCMs), particularly focusing on adherens junctions. CCM is a vascular disease that affects specifically the venous microvessels of the central nervous system and which is caused by loss-of-function mutation in any one of the three CCM genes (CCM1, 2 or 3) in endothelial cells. The phenotypic result of these mutations are focal vascular malformations that are permeable and fragile causing neurological symptoms and occasionally haemorrhagic stroke. Recent findings CCM is still an incurable disease, as no pharmacological treatment is available, besides surgery. The definition of the molecular alterations ensuing loss of function mutation of CCM genes is contributing to orientate the testing of targeted pharmacological tools.Several signalling pathways are altered in the three genotypes in a similar way and concur in the acquisition of mesenchymal markers in endothelial cells. However, also genotype-specific defects are reported, in particular for the CCM1 and CCM3 mutation. Summary Besides the specific CCM disease, the characterization of endothelial alterations in CCM has the potentiality to shed light on basic molecular regulations as the acquisition and maintenance of organ and vascular site specificity of endothelial cells.
- Subjects :
- 0301 basic medicine
Pathology
medicine.medical_specialty
Hemangioma, Cavernous, Central Nervous System
Central nervous system
Disease
medicine.disease_cause
Exocytosis
Adherens junction
Translational Research, Biomedical
03 medical and health sciences
Proto-Oncogene Proteins
medicine
Animals
Humans
Mutation
business.industry
Vascular disease
Mesenchymal stem cell
Endothelial Cells
Hematology
Adherens Junctions
medicine.disease
Phenotype
Endothelial stem cell
030104 developmental biology
medicine.anatomical_structure
business
Angiopoietins
Biomarkers
Signal Transduction
Transcription Factors
Subjects
Details
- ISSN :
- 15317048
- Volume :
- 24
- Issue :
- 3
- Database :
- OpenAIRE
- Journal :
- Current opinion in hematology
- Accession number :
- edsair.doi.dedup.....f52a03f249ea8e6ad8e60fd7a2ad3ea8