Wake Forest University School of Medicine has received a $2.5 million grant from the National Heart, Lung and Blood Institute, part of the National Institutes of Health, to study heart failure with preserved ejection fraction (HFpEF). The five-year project, led by Pooja Jadiya, Ph.D., assistant professor of internal medicine, focuses on how different heart cells handle calcium inside their mitochondria, a process that may drive the disease.
HFpEF accounts for nearly half of all heart failure cases. In this form, the heart pumps normally but becomes too stiff to fill with blood, leading to fatigue, swelling and shortness of breath. Treatment options remain limited, and few address the root cause.
“Most people think of heart failure as one disease, but there are different types,” Jadiya said. “In HFpEF, the heart does pump normally, it just can’t fill properly. Current therapies primarily manage symptoms such as swelling or blood pressure. They don’t fix the cellular or molecular causes.”
Mitochondrial calcium plays a central role in how heart cells make energy. Proteins on mitochondrial channels regulate how much calcium flows in. When those proteins fail, calcium levels fall out of balance.
Those imbalances may look different in different types of heart cells.
“The heart isn’t made of only muscle cells,” Jadiya said. “Fibroblasts and endothelial cells also play major roles, and each uses energy differently. If one cell type goes wrong, it can affect the others.”
The study will examine three cell types (cardiomyocytes, fibroblasts and endothelial cells) by comparing healthy hearts to those affected by HFpEF. The team will then adjust calcium handling in specific cell types to test whether correcting the imbalance improves heart function.
A key hurdle is separating mitochondria from different cells in the same tissue. Jadiya’s team will use a harmless virus that acts like a label maker, tagging mitochondria only in the cell type they want to study.
“That way, we can isolate and analyze mitochondria from specific cells directly from living heart tissue,” Jadiya said. It’s a very powerful and precise approach.”
If certain cell types show greater calcium dysregulation, future therapies could target only those cells.
“Our goal is to show that targeting the right cells in the right way can reverse heart failure symptoms, not just manage them,” Jadiya said. “If we succeed, it could lead to therapies that address the root cause inside the heart cells therapies that would help patients breathe easier, have more energy and live longer, healthier lives.”
The work challenges the common assumption that mitochondrial calcium problems affect all heart cells equally. Jadiya believes each cell type handles calcium differently, depending on its function and environment. Effective therapies will need to account for those differences.
“I hope people remember this research as the point where we began thinking about the heart not as a single organ, but as a community of different cells,” Jadiya said. “If we can treat the heart at the level of individual cells, we can discover a more effective way to heal and prevent this disease.”
Researchers at Wake Forest University School of Medicine, the academic core of Advocate Health, together with colleagues across the Advocate Health heart and vascular national service line, advance care through groundbreaking research and clinical innovation nationwide. As a national leader in clinical research, we’re pioneering breakthroughs to prevent disease, deliver earlier diagnoses and transform treatment for better patient outcomes.