The sarcoplasmic reticulum (SR) is a membrane-bound structure found within the cardiac muscle cells. Its main function is to regulate the flow of calcium, releasing calcium ions to the surrounding muscle fibers during contraction of the heart muscle and absorbing calcium during relaxation; calcium makes the heart pump. A crucial protein that regulates the function of the SR is phospholamban (PLN); mutations in the PLN gene result in defective PLN which can in turn causes a genetic, or inherited, form of heart failure.

The CURE-PLaN network will focus on one particular mutation that is found in patients in the United States and Europe. Our objective is to understand how patients with the mutation develop heart failure, and why not all patients with the mutation have the same clinical course.

Network scientists will use various models and single muscle cell lines to learn more about the genetics of the disease and how to alter the SR and PLN to make heart muscle cells work more efficiently. This network is funded by the Leducq Foundation and will work with the Dutch PLN Patient Foundation to focus on combatting PLN induced heart failure. Our ultimate goal is to cure PLN induced heart failure in humans.