Key protein critical in maintaining heart health

No one can live without a heart pumping blood to the rest of the body. New research from the University of Missouri School of Medicine reveals more information about this vital function and how it’s related to certain heart diseases and conditions.

In a heartbeat, cardiac muscle cells contract to push blood out to the body, then relax to allow the heart to fill again. This is possible because muscle proteins are organized into sarcomeres, which are small structural units of muscle located inside muscle cells. When a muscle contracts, the parts of a sarcomere “shorten” and come closer together. Each cardiac muscle cell can have over 5,000 sarcomeres, which compounds both the shortening and relaxation events.

“This process appears to be regulated by myosin binding protein-C (cMyBP-C), which is a heart muscle protein,” study author Kerry McDonald said. “Our study investigated its role in cardiac muscle contraction. Without this protein, muscles contraction occurred at a higher rate, especially when the heart was under increased stress.”

According to the research, the protein seems to sense stress on the muscle cells and adjusts sarcomere shortening – and consequently, muscle contraction – based on how hard the heart needs to work. If cMyBP-C is not present or is mutated, it decreases the cell’s ability to properly adjust the strength of muscle contraction.

“This protein seems fundamental to heart performance and cardiovascular health,” McDonald said. “In fact, alterations to this protein are linked to diseases like heart failure and hypertropic cardiomyopathy (HCM).”

HCM is a condition where cardiac muscles become thicker than usual, which makes it harder for the heart to pump blood and to fully relax, causing the muscles to contract more often. Mavacamten, a recently developed medication, helps treat HCM and could treat other cardiac-related diseases. 

The medication targets sarcomeres and reduces their activity, which then reduces the rate of cardiac muscle contraction. In the study, mavacamten was useful in mice without cMyBP-C for regulating the sarcomere shortening process. 

“This study demonstrates the potential benefit of focusing on cMyBP-C in targeted therapies, which can improve quality of life for patients with heart disease,” McDonald said. 

Kerry McDonald, PhD is a professor and the chair of Medical Pharmacology and Physiology at the Mizzou School of Medicine. He is also a Bolm Distinguished Professor, and a Bolm Distinguished Chair in Cardiovascular Health. 

“Myosin binding protein-C modulates loaded sarcomere shortening in rodent permeabilized cardiac myocytes” was recently published in the Journal of General Physiology. In addition to McDonald, Mizzou study authors include Theodore Kalogeris, PhD, assistant research professor of Medical Pharmacology and Physiology; Adam Veteto, PhD, application scientist with the Department of Medical Pharmacology and Physiology; Daniel Davis, PhD, assistant director of the MU Animal Modeling Core; and Laurin Hanft, PhD, assistant teaching professor of Medical Pharmacology and Physiology.