LONDON / RankWire.AI / – Researchers at King’s College London have discovered a naturally occurring compound that improved critical indicators of heart function in experimental models of heart failure with preserved ejection fraction, or HFpEF. In animal studies, urolithin A enhanced some measures by as much as 80% compared to untreated controls. Additionally, the compound facilitated better relaxation of heart tissue, decreased scarring, and limited harmful expansion of heart muscle cells. The team also observed improved relaxation in engineered human heart tissue derived from stem cells.
HFpEF is characterized by the heart maintaining a normal or nearly normal ejection fraction but experiencing difficulty relaxing and filling properly between beats. Patients with this condition often suffer from breathlessness, fatigue, and reduced exercise capacity. According to the British Heart Foundation, it accounts for nearly half of all heart failure cases in the UK. Urolithin A forms within the body when gut bacteria process compounds found in foods like pomegranates, walnuts, and certain berries, although its production varies from person to person.
The research team found that urolithin A targets a protein called PKGIα, which is involved in blood vessel regulation and heart muscle relaxation. The compound directly modifies cysteine 42, a specific amino acid on the protein, and activates 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. The work was led by researchers from King’s College London, with Joseph Burgoyne serving as the senior author.
Compound decreased fibrosis and prevented abnormal heart enlargement
In the animal model, urolithin A improved diastolic function, which measures the heart’s ability to relax and fill with blood. The researchers also noted a reduction in fibrosis, the buildup of scar tissue that can impair normal cardiac performance. Treatment additionally lessened the enlargement of heart muscle cells in comparison to untreated controls. The reported improvement of up to 80% applied to specific measures of heart function within the experimental setting. This does not imply an 80% improvement in patients or an 80% reduction in heart failure incidence.
Further testing involved engineered human heart tissue derived from stem cells, which emulate important features of human cardiac muscle. This model allowed researchers to assess contraction and relaxation under controlled laboratory conditions. Urolithin A demonstrated improvements in both relaxation and contraction kinetics in this tissue. The researchers highlighted that urolithin A has already been evaluated in human studies for other purposes and has shown a favorable safety profile. However, the HFpEF findings stem from animal experiments and tissue models rather than clinical trials involving patients.
Further clinical validation in heart failure patients remains essential
British Heart Foundation, which funded the investigation, stated that these preliminary results suggest urolithin A could improve the heart tissue’s ability to relax and fill between beats. Nonetheless, they emphasized that benefits in humans with HFpEF have yet to be demonstrated. Similarly, King’s College London cautioned against interpreting these findings as evidence that consuming pomegranates can treat heart failure. No single food has been proven by this research to prevent or cure the condition.
The study highlights PKGIα cysteine 42 as a promising biological target for further HFpEF research and demonstrates how urolithin A activates this pathway in experimental systems. HFpEF remains a significant form of heart failure often associated with conditions such as high blood pressure, obesity, and diabetes. The findings offer molecular insights into how heart relaxation may be modulated through this mechanism. Clinical trials involving patients are necessary to determine if urolithin A can safely and effectively produce similar outcomes in individuals with HFpEF.