VDAC2 Protein Could Play Role in Heart Failure Prevention

A protein that helps regulate calcium signaling within heart cells could play a key role in preventing chronic heart failure, according to an international study led by University of Utah Health scientists. The researchers say disruption in the signaling pathway for this protein, VDAC2, causes severe impairment of heart cell contraction, making it harder for the heart to deliver blood to the body. The findings, published in Nature Communications, suggest that drugs and other therapeutic treatments targeting VDAC2 could eventually help alleviate heart failure.

“Based on our human and laboratory research, it appears that If VDAC2 is not working properly, then everything in the heart can cascade down from there,” says Stavros Drakos, senior author of the study. “If we can figure out ways to help this protein do its job again, then it’s possible that we might be able to address heart failure far earlier in the disease process.”  

In their study, Drakos and colleagues sought to get a better understanding of mitochondria’s role in the calcium cycle within heart cells. First, the team knocked out VDAC2 in mouse models. Without it, calcium flow in the mitochondria was severely impaired, and heart cells couldn’t beat properly. The mice also developed enlargement of the heart’s left ventricle or pumping chamber. This condition, called dilated cardiomyopathy, made it harder for the heart to pump blood and eventually led to heart failure and death.

Specifically, the researchers found that VDAC2 interacts with a pair of proteins in the sarcoplasmic reticulum. Hindering this protein-to-protein communication leads to impaired cellular calcium signaling and heart failure. However, restoring VDAC2 in knock-out mice reversed many of the effects of heart failure, including reduced swelling of the left ventricle, and prevented death. “Our study shows the importance of VDAC2 in normal cardiac function,” says Thirupura Sundari Shankar, lead author of the study. “Through this unique role, VDAC2 emerges as a potential therapeutic target for heart failure patients.”