An artery is not just a tube that blood flows through. Its wall contains living cells that contract and relax, helping to push the blood along. But sometimes these cells take on a completely different job: they deposit calcium, and the soft, elastic artery becomes as stiff as bone. That is dangerous, because a stiff vessel can rupture or become blocked.
Why does the cell do this? It turns out there is a special protein complex inside it that works like a bookmark in a book. It shows the cell which pages of its genetic instruction manual need to be read. Under stress, for instance when there is too much calcium around, this complex changes its composition and starts switching on the genes needed to build bone. The protein ETS2 works alongside it, amplifying the signal.
Scientists tested this in human cells. When they turned off the proteins of this complex, the calcium stopped being deposited. And in the arteries of people with atherosclerosis, these "switched" cells were found next to immune cells that arrive at the site of damage. Perhaps it is these immune cells that give the signal to retrain.
Now that the switch is known, it can be targeted. Drugs that interfere with the complex already exist. Give them in time, and the artery stays soft, while the cell does not forget its real job.
The protein BRD9 is named after its bromodomain, a pocket that recognizes acetylated lysines on histones. The inhibitor I-BRD9 occupies this pocket like a key inserted into a lock, preventing the complex from landing on chromatin.
The idea of 'reprogramming' cells in an adult body recalls the plot of the movie Total Recall, where implanted memories change a person's identity. Here an epigenetic complex changes the cell's 'memory' of its profession, forcing a contractile cell to become a bone builder.
Not published on arXiv. Here are its page, the PDF and the formalization: you can check it yourself, not only read our account.