Washington, September 3 (ANI): Scientist at the University of California, San Francisco (UNSF) say that irregularities in a constantly active Notch gene in endothelial brain cells may cause a vascular disorder that causes stroke.
The researchers say that their experiments on mice are the first to provide information on both the progression and regression of the brain disorder BAVM, in which arteries and veins get connected directly rather than through capillaries.
The direct connection produces enlarged, tangled masses of vessels that are prone to hemorrhagic rupture, bleeding, and stroke.
During the study, the researchers used genetic tools to "turn on" the Notch gene, which induced BAVM. When the researchers turned the gene off, the mice exhibited full recovery from the disease's progression.
"This was exciting. The activated Notch gene caused BAVM in all of the mice, making it an unprecedented, potent molecular lesion in the induction of the pathology. Furthermore, we found that repression of the gene in already-ill mice led to their recovery," said Rong Wang, senior author on the study, associate professor and director of the Laboratory for Accelerated Vascular Research and Mildred V. Strouss Endowed Chair in Vascular Surgery at UCSF.
Patrick A. Murphy, lead author on the paper and a graduate student from the UCSF Biomedical Science Program, added: "Our study offers hope for future treatments because even the effects of stroke such as paralysis and ataxia, or loss of muscle coordination, were reversed once we turned off Notch. This pathway has not yet been implicated in human disease, so these findings prompted our ongoing research into Notch signaling and allow us to examine the cellular and molecular mechanisms of BAVM."
The researchers believe that the knowledge gained about the development of BAVM may also be helpful in understanding the process of blood vessel disease in other organs like the lung and liver.
"In the future, we may be able to inhibit or even reverse the disease process," said Tyson Kim, co-author on the paper and a bioengineering graduate student from the UCSF MD/PhD combined program, working with Wang.
The researchers now consider Notch a strong candidate as a key regulator of human BAVM, and are undertaking additional research to find the disease's cause.
Besides studying disease progression and regression in mouse models, the researchers are also looking at the gene's role in human AVMs by examining levels of Notch signalling pathway molecules in surgical tissue samples.
"Although more work needs to be done to determine whether the research can be applied to clinical practice and whether up-regulation of Notch causes BAVM and stroke in humans, identifying the role of this pathway offers hope for developing treatments for this and other related diseases," Wang said.
The study has been published in the Proceedings of the National Academy of Sciences. (ANI)
|
|
Comments:
