By Tanner Lambson

New research from the VCU Health Pauley Heart Center and Virginia Commonwealth University's School of Medicine is providing new insights into the molecular underpinnings of heart failure.

Published this month in Circulation, the findings shed light on a newly discovered metabolic pathway that contributes to heart injury. The study found that an enzyme known as SPTLC3 is detected in the cells of hearts that have experienced heart failure due to a decrease in blood supply to heart tissues (as occurs during a heart attack). This type of heart failure is referred to as ischemic heart failure.

The research team made the initial discoveries in a mouse model, finding that when production of SPTLC3 was limited, related cellular symptoms of heart failure — such as inflammation and scarring — were also reduced. Importantly, these findings were then validated and confirmed in cardiac tissues from patients with end-stage ischemic heart failure, leading to the conclusion that SPTLC3 may exert a previously unrecognized impact on the heart metabolism following a heart attack.

What this means is that inhibiting SPTLC3 may serve as a new therapeutic target to improve health outcomes in patients with ischemic heart failure.

Ischemic heart disease occurs when blood flow to the heart is reduced, usually due to arteries that are narrowed or obstructed by a buildup of plaques. When coronary blood flow is reduced, the flow of oxygen and nutrients to heart muscle cells is also reduced, and the heart cannot work as it should. Reduced blood flow and concurrent oxygen deprivation can ultimately lead to heart attack, and SPTLC3 may play an important role in the damage that occurs to cells after heart attack.

The study arose from a collaboration between Ashley Cowart, Ph.D., a professor in the VCU School of Medicine’s Department of Biochemistry and Molecular Biology and director of VCU’s Lipidomics and Metabolomics Shared Research core, and Fadi Salloum, Ph.D., FAHA, interim chair of the School of Medicine’s Department of Physiology and Biophysics and the Natalie N. and John R. Congdon Sr. Endowed Chair in the Pauley Heart Center.

“VCU has historical strength in both lipid research and cardiovascular research,” Cowart said. “A major strength of this work is rooted in our collaboration across these two fields. We were able to combine expertise and cutting-edge technologies in both cardiac imaging and lipid biochemistry. Additionally, the Pauley Heart Center’s tissue repository enabled us to link our findings to human health.”

“Bringing together researchers from different scientific backgrounds is what we do at the Pauley Heart Center,” Salloum said. “We collaborate across departments and schools at VCU to advance discovery in cardiovascular medicine.”

Together, Cowart and Salloum conceptualized the research and mentored the lead author of the publication, Anna Kovilakath, Ph.D., who is now a T32 postdoctoral fellow at Pauley Heart Center. She carried out the majority of the study with the help and guidance of Gabriele Mauro, Ph.D., who recently completed his postdoctoral fellowship in the Salloum laboratory.

Kovilakath says she is motivated to research the intricacies of heart disease because of personal connections to this health condition.

“Having lost family to cardiovascular disease, I've chosen to dedicate my career to studying sphingolipids in the context of heart disease,” Kovilakath said. “It's a meaningful way for me to contribute to understanding and combating this global health issue."

Training the next generation of practitioners and researchers is a key part of what sets Pauley apart.

“Mentorship is something we do really well here — and you can see that in the retention of our talented trainees,” Salloum said.

Other key collaborators from the Pauley Heart Center include Ed Lesnefsky, M.D., Qun Chen, Ph.D., and Frank Raucci, M.D., Ph.D., from Children’s Hospital of Richmond at VCU.