Blood vessel deformities start in vein cells

Overview

• Post By : Kumar Jeetendra


• Source: Uppsala University


• Date: 03 Nov,2020

In the condition called cavernoma, lesions appear in a cluster of blood vessels in the brain, spinal cord or retina. Researchers from Uppsala University can now reveal, at molecular level, these changes originate in vein cells. This new understanding of the condition creates possibility of developing better treatments for patients. The study was published in the journal eLife.

The vascular lesions, or blood-vessel malformations, that appear in a cerebral cavernoma – also called a cerebral cavernous malformation (CCM) or, in america, cavernous angioma – resemble mulberries. They bleed easily, which might cause epileptic attack, neurological problems and stroke. The condition is due to genetic mutations that may be inherited or occur spontaneously, and is incurable at present. Surgery is an option but, in patients with the hereditary type in whom new CCMs arise continuously, only a temporary solution.

One of the genes that may mutate in the inherited form of CCM is called CCM3. We’ve examined mouse brain endothelial cells, after specific endothelial deletion of CCM3. The cells were clustered in venous and arterial endothelial cells, and we were able to see that venous endothelial cells were particularly sensitive to loss of the CCM3 gene.”

Peetra Magnusson, Department of Immunology, Genetics and Pathology (IGP)

How, and in which sort of blood vessel, the mutations occur has not been entirely clarified to date. In the current study, the researchers at Uppsala University – in collaboration with IFOM, the FIRC Institute of Molecular Oncology, and the Mario Negri Institute of Pharmacological Research in Italy – researched endothelial cells. The role of these cells, which line the interior of blood vessels, varies based on vessel type, leading to the differing features of veins, arteries and capillaries. In all, the scientists have analysed more than 30,000 individual endothelial cells in detail to identify how, and in which vessels, CCMs appear.

When CCM3 was lacking in mural endothelial cells of the venous type, the researchers observed increased cell division and abnormal development of the vessels, resulting in the characteristic mulberry-like lesions. The study thus confirms, at molecular level, the vascular malformations of a cavernoma arise in veins. This was observed previously only when the structure of the blood vessels had been analyzed in vessel fragments.

“Another interesting result from the study was that arterial endothelial cells were not affected at all in the identical way by losing their CCM3. Although the CCM3 gene was missing in these cells, they do not contribute to growth of the malformations,” says Elisabetta Dejana, who led the study.

“Summing up, our findings also have brought new understanding about cavernoma, which should enhance the odds of developing improved clinical treatments.”