The lub-dub of a healthy heart pg. 5
Barnett and Galper followed gene expression and protein changes at a particular stage in chick heart development to discover how the heart muscle begins to respond to hormones that regulate heart rate. Before day 3, drugs that normally change the heart rate have no effect; in the next day or so, “those systems come online, and you’ve got a heart that behaves like an adult heart,” Barnett says.
As Barnett was finishing up his postdoctoral studies, a chance elevator conversation with Maas, a friend from graduate school at Vanderbilt, led to a collaboration between the two that kindled Barnett’s interest in how the heart’s structure forms.
He began to pursue the role of TGF-beta, a widely expressed growth factor involved in cell proliferation and maturation. It was first described in the early 1980s by Mayo Clinic researchers led by Harold Moses, M.D., who later directed the Vanderbilt-Ingram Cancer Center.
TGF-beta also is one of the factors that Barnett and Galper identified as key to turning on the hormone response in chick heart muscle. At Vanderbilt, Barnett and colleagues found that a particular TGF-beta receptor – the type III receptor – is essential for the transformation of endocardial cells in early heart valve formation.
Interestingly, the chromosomal region that is home to the type III TGF-beta receptor gene has been linked to congenital defects in the valves and dividing walls of the heart. Other scientists are looking for the variants that cause the defects.