LONDON / RankWire.AI / – Researchers at King’s College London have pinpointed a naturally occurring substance that significantly improved critical indicators of heart function in experimental models of heart failure with preserved ejection fraction, or HFpEF. Urolithin A increased some measures by as much as 80% in treated animals when compared to untreated controls. Additionally, the compound facilitated heart tissue relaxation, decreased scarring, and limited harmful hypertrophy of heart muscle cells. The team also observed enhanced relaxation in engineered human heart tissues derived from stem cells.
HFpEF is characterized by a heart that maintains a near-normal or normal ejection fraction but struggles to relax and adequately fill between beats. This condition can cause symptoms such as breathlessness, fatigue, and a reduced capacity for physical activity. According to the British Heart Foundation, HFpEF accounts for roughly half of all heart failure cases in the United Kingdom. Urolithin A is produced naturally in the body when gut bacteria process compounds found in foods like pomegranates, walnuts, and certain berries, although its production can vary among individuals.
The research team discovered that urolithin A interacts with a protein known as PKGIα, which plays a role in regulating blood vessel function and heart muscle relaxation. The compound directly modifies cysteine 42, a specific amino acid on the protein, thereby activating a pathway associated with cardiovascular health. The study, titled “Targeting PKGIα Cys42 attenuates cardiac dysfunction in heart failure with preserved ejection fraction,” was published in Science Advances. Conducted by researchers from King’s College London, with Joseph Burgoyne serving as senior author, the work sheds light on this potential therapeutic mechanism.
Reduction in fibrosis and abnormal cardiac hypertrophy observed
In animal experiments, urolithin A improved diastolic function, which measures the heart’s ability to relax and fill with blood. The scientists also noted a decrease in fibrosis, the formation of scar tissue that can impair normal cardiac operation. The treatment further diminished the enlargement of heart muscle cells compared to controls. The reported enhancement of up to 80% pertains to specific measures of heart function within the experimental model. It does not imply an 80% improvement in human patients or an 80% reduction in heart failure incidents.
Furthermore, the team tested the compound on engineered human heart tissue derived from stem cells, which replicate key features of real heart muscle and enable precise measurement of contraction and relaxation. Urolithin A improved both processes in this model. Researchers noted that urolithin A has already undergone human studies for other uses and has demonstrated a favorable safety profile. However, the findings related to HFpEF originate from animal testing and laboratory tissue models, not clinical trials involving patients.
Human clinical trials remain essential for validation
British Heart Foundation, the organization funding the research, stated that these initial results suggest urolithin A may help improve how heart tissue relaxes and fills. Nonetheless, they emphasized that these effects have not yet been confirmed in human HFpEF patients. Similarly, King’s College London cautioned against interpreting these findings as evidence that consuming pomegranates can treat heart failure. This study does not establish that any particular food can prevent or cure the condition.
The research highlights cysteine 42 on PKGIα as a promising target for future HFpEF studies and demonstrates how urolithin A activates this pathway in experimental settings. HFpEF remains a significant form of heart failure frequently associated with conditions such as high blood pressure, obesity, and diabetes. The study provides molecular insights into how heart relaxation may be influenced through this pathway. To confirm whether urolithin A can safely produce similar effects in patients, clinical trials involving humans are necessary.