What’s behind a risky cellular shift
Yale scientists have pieced together a molecular program that sustains endothelial cells, which line blood vessels throughout the body. Researchers had proposed only recently that in a process called Endo-MT, these cells transition into another type, mesenchymal cells, which prompt the buildup of scar tissue in vessel walls, heart valves, and other tissues. The Endo-MT shift is suspected to play a role in many conditions, including atherosclerosis and hypertension, but it wasn’t fully understood how the change takes place.
In the December 27, 2012 issue of Cell Reports, a team led by Michael Simons, M.D., Robert W. Berliner Professor of Medicine and section chief of cardiovascular medicine, shows that a signaling molecule called fibroblast growth factor (FGF) maintains levels of let-7, a snippet of genetic material known as a microRNA. In turn, let-7 puts the brakes on expression of the receptor for a signaling molecule called transforming growth factor beta (TGF-ß). When TGF-ß binds to its receptor it directly induces Endo-MT, so when FGF expression was blocked, let-7 levels plummeted, and TGF-ß did its damage.
“The loss of FGF signaling input may be the root cause of a number of the most common cardiovascular illnesses,” says Simons.