Research Story Tip: Poor Energy Metabolism May Drive Heart Failure after Attack

11/24/2020

After a heart attack, a patient can go on to develop cardiac failure, but not always. Previous research looking at the molecular mechanism behind this process in heart muscle cells showed that the heart enzyme calmodulin kinase II (CaMKII) relocates to the power factories of the cell — the mitochondria — shortly after a heart attack to drive the organ’s shutdown.

Now, Johns Hopkins Medicine researchers have shown in mice that CaMKII drains energy molecules from the mitochondria of heart muscle cells, causing the heart to work harder because it doesn’t pump as efficiently. They also revealed that it was possible to direct an enzyme to move energy out of the mitochondria, enabling it to fuel the heart muscle cells. In turn, they say, this prevents the physical signs of failure in mouse hearts.

The findings, published on Sept. 4, 2020, in Nature Communications, suggest that by targeting energy transfer in the heart’s muscle cells, it may be possible to prevent the progression to cardiac failure following a heart attack.

“It's really not clear clinically why certain people who have heart disease will progress to heart failure while others won't,” says Elizabeth “Betsy” Luczak, Ph.D., assistant professor of medicine at the Johns Hopkins University School of Medicine, and lead author of the study. “Our findings suggest this could be a clue as to the ways to develop a therapy for people with dilated heart failure or even arrhythmias [irregular heartbeats] by enhancing transfer of ATP, the energy molecules in the cell.”

Following a heart attack, one of the classic signs of heart failure is when the left ventricle — the chamber of the heart responsible for pumping oxygenated blood throughout the body — increases in size from working too hard. This is because the tissue of the ventricle thins and doesn’t pump as well. In their study using a mouse model of a heart attack, Luczak and her colleagues turned on the enzyme creatine kinase to high levels in the heart muscle, which prevented CaMKII from draining ATP and resulted in the left ventricle no longer dilating and thinning.

According to the U.S. Centers for Disease Control and Prevention, heart failure eventually leads to death, with more than half of patients dying within five years of developing the condition.