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In cerebral cavernoma, lesions develop in a group of blood vessels in the brain, spinal cord, or retina. Researchers at Uppsala University can now demonstrate at the molecular level that these changes originate in venous cells.
Special role of the CCM3
In cerebral cavernoma, lesions develop in a group of blood vessels in the brain, spinal cord, or retina. Uppsala University researchers can now demonstrate on a molecular level that these changes originate in venous cells. This new knowledge of the disease creates the potential for developing better therapies for patients. The study was published in the journal eLife.
How and in what type of blood vessels mutations in brain cavernomas occur has not yet been fully understood. In a recent study, researchers from the University of Uppsala – in collaboration with IFOM, the FIRC Institute of Molecular Oncology and the Mario Negri Institute for Pharmacological Research in Italy – examined endothelial cells. The function of these cells varies according to the type of vessel and contributes to the different properties of arteries, veins and capillaries. In total, the researchers detailed more than 30,000 individual endothelial cells to find out how and in which vessels CCMs occur.
“One of the genes that can mutate in the hereditary form of CCM is called CCM3. We examined mouse brain endothelial cells for a specific CCM3 endothelial deletion. The cells were clustered into venous and arterial endothelial cells and we could see that the cells Venous endothelials in particular are sensitive to loss of the CCM3 gene, “says Peetra Magnusson of the Department of Immunology, Genetics and Pathology (PGI).
Increased cell division and abnormal vessel growth in the absence of CCM3 in the endothelial cells of the wall
When CCM3 was not present in venous-type wall endothelial cells, the researchers observed increased cell division and abnormal vessel growth, which led to the characteristic mulberry-like lesions. The study therefore confirms at the molecular level that the vascular malformations of a cavernoma arise in the veins. Until now, this has only been recognized by examining the structure of the blood vessels in the vascular fragments.
“Another interesting result of the study was that arterial endothelial cells were not affected in the same way by the loss of their CCM3. Although the CCM3 gene was also absent in these cells, they did not contribute to the development of malformations,” says Elisabetta Dejana. who directed the study. “In summary, our results have provided new insight into cavernomas that should lead to better clinical treatments.”
Those:
Fabrizio Orsenigo et al. (2020), Mapping the diversity of endothelial cells in brain cavernous malformations at single cell resolution, eLife.
eLife 2020; 9: e61413; DOI: 10.7554 / eLife.61413
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