In the wall of every vessel there are cells that work as builders and power plants at once. They make a tough scaffold out of the protein collagen, hold their shape with internal filaments and extract energy from sugar. Their boss is the NOTCH3 protein, which sits on the cell surface and receives signals from its neighbours. Switch this protein off and the cells do not die, but they start working differently.
Scientists took cells from the human aorta and switched off the NOTCH3 gene in them using short RNAs. After a few days the protein was down by 83-87%. The cells stayed alive and kept dividing. But they also started producing more collagen, especially type III collagen. It is as if builders, having lost their foreman, decided to reinforce the walls just in case.
This experiment matters for CADASIL, a disease in which small vessels of the brain suffer because of a faulty NOTCH3 gene. Researchers used to think the problem was too little protein. Now it is clear that simply removing NOTCH3 does not break the cell, even though it changes how the cell works. So in this disease the harm comes not from a shortage of the protein but from its wrong shape. Treatment should remove the bad copy rather than simply add a good one. That is how scientists tested how safe it is to interfere with this conductor.
The NOTCH3 protein got its name from a mutation in Drosophila: flies with a defect in this gene had wings with a jagged edge resembling a notch. In humans, the same protein turned out to be key for blood vessel walls, and when it breaks down it causes hereditary strokes.
Not published on arXiv. Here are its page, the PDF and the formalization: you can check it yourself, not only read our account.