Cardiovascular disease is one of the leading causes of death in the Western world. Calcium metabolism is a key process within the heart muscle as it contributes not only to the electrical activity of the heart, but also and above all to the generation of electrical activity in the heart muscle cells. Here, calcium metabolism is regulated by the so-called L-type calcium channel. This channel plays a crucial role in both healthy and diseased hearts and is a target for various therapeutic approaches.
A team of researchers led by cardiologist Dr. med. Matthias Eden and Professor Dr. Norbert Frey at the University Medical Center Schleswig-Holstein in Kiel, together with partners in Heidelberg and Munich, have for the first time succeeded in comprehensively characterizing a novel cardiac muscle protein known as “Myoscape”, thereby unlocking a new mechanism that plays a central role in the development and progression of heart failure. The findings of their basic research were published in a recent edition of the leading scientific journal Nature Communications. The investigators were able to show that Myoscape binds to the L-type calcium channel, together with the actinin 2 protein, thus significantly influencing its function through adherence to the cell membrane. When Myoscape was lacking a serious disruption of the calcium metabolism developed, not only in the isolated heart muscle cells, but in a genetically engineered mouse line as well, ultimately leading to progressive heart failure. In addition, the team successfully demonstrated that artificially increasing the quantity of Myoscape protein in the myocardial cells significantly improved calcium cycling and even has the potential to restore disrupted calcium cycling in failing myocardial cells. Because the hearts of patients with heart failure contain reduced amounts of Myoscape protein, the investigators now believe to have found an important new mechanism in the development of heart failure, and possibly also a target for future treatment strategies.