Examine light on the features of pathology behind sudden cardiac death

Nearly half a million people each year die from sudden cardiac death (SCD) in the U.S. – the result of malfunctions in the electrical system of the heart.

The main cause of SCD in young athletes is arrhythmogenic cardiomyopathy (ACM), a genetic disease in which scar muscle (fibrosis) and fat replace healthy heart muscles over time.

Stephen Chelko, assistant professor of biochemical sciences at Florida State University College of Medicine, has gained a better understanding of the pathological features behind the disease, as well as promising pathways for prevention. His findings are published in the current issue of Science Translational Medicine.

Mutation in people with ACM causes arrhythmias, which are usually non-fatal if properly managed and treated. However, Chelko shows that exercise not only increases these arrhythmias, but causes widespread cell death. Their only option is to avoid participating in an effort that should be healthy and worthwhile: exercise.

There is some horrible irony in that exercise, a known health benefit to the heart, leading to cell death in ACM subjects. Now, we know that endurance exercise, in particular, leads to large-scale myocyte cell death as a result of mitochondrial dysfunction in those suffering from this hereditary heart disease. “

Stephen Chelko, Associate Professor of Biomedical Sciences, College of Medicine, Florida State University

Almost every cell in the body contains several thousand mitochondria, processing oxygen and converting food into energy. Considered to be the energy power of every cell (they produce 90 percent of the energy our bodies need to function properly), they also play another important role as a protective antioxidant.

Because mitochondria do not work properly, and myocyte cells in the heart die, scar muscle and fat cells are replaced. Eventually, the heart’s normal electrical signals are reduced to irregular burning of impulses from the lower chambers, leading to an inability to pump blood properly during strenuous exercise. Without immediate medical treatment, death occurs within minutes.

Chelko’s research gets to the heart of the process involved in mitochondrial dysfunction.

“Eventually, mitochondria gain excess weight and eliminate‘ death signals ’that are sent to the nucleus, initiating large-scale DNA breakdown and cell death,” Chelko said. “This novel study unlocks a pathogenic pathway for exercise-induced, mitochondrial-induced cell death in ACM hearts.”

In addition to providing a better understanding of the process involved, Chelko found that cell death can be prevented by inhibiting two different mitochondrial proteins. One such approach uses a novel targeting peptide developed for Chelko research by the National Research Council in Padova, Italy.

That discovery opens avenues for developing new therapeutic options to prevent myocyte cell death, heart disorder and the pathological progression leading to fatal consequences for people living with ACM.