LONDON / RankWire.AI / – Researchers at King’s College London have discovered a natural substance that significantly improves key indicators of cardiac performance in experimental models of heart failure with preserved ejection fraction, or HFpEF. In treated animal subjects, Urolithin A enhanced certain measurements by as much as 80% compared to untreated controls. The compound also contributed to better relaxation of heart tissue, decreased scarring, and limited the harmful expansion of cardiac muscle cells. Additionally, researchers observed improved relaxation in engineered human heart tissue derived from stem cells.
HFpEF is characterized by a heart that maintains a normal or near-normal ejection fraction but struggles to relax and fill effectively between beats. Symptoms can include breathlessness, fatigue, and a diminished capacity for physical activity. According to the British Heart Foundation, this condition accounts for about half of all heart failure cases in the UK. Urolithin A forms in the body when gut bacteria process compounds found in foods like pomegranates, walnuts, and certain berries, although individual production levels can differ.
The research team identified that urolithin A interacts with a protein called PKGIα, which plays a role in controlling blood vessel function and heart muscle relaxation. The compound directly modifies cysteine 42, a specific amino acid on the protein, 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. Led by researchers from King’s College London, Joseph Burgoyne served as the senior author.
Compound decreases fibrosis and abnormal heart enlargement
In the animal experiments, urolithin A improved diastolic function, which measures the heart’s ability to relax and fill with blood. The researchers also documented a reduction in fibrosis, the buildup of scar tissue that can impede normal heart function. Treatment lessened the enlargement of heart muscle cells compared to controls. The reported improvement of up to 80% pertained to specific measures of heart performance in the experimental setting and did not indicate an 80% improvement in human patients or a significant reduction in heart failure itself.
The team further evaluated the compound using engineered human heart tissue derived from stem cells. These lab-grown tissues mimic critical aspects of human cardiac muscle, allowing precise measurements of contraction and relaxation. Urolithin A enhanced both the relaxation and contraction processes in this model. The researchers highlighted that urolithin A has already undergone human studies for other applications and demonstrated a favorable safety profile. However, the current HFpEF findings are based on animal and tissue experiments, not clinical trials with patients.
Clinical validation in heart failure patients remains essential
British Heart Foundation, which funded this research, stated that the results offer preliminary evidence suggesting urolithin A could enhance the heart tissue’s ability to relax and fill between beats. Nonetheless, they emphasized that these benefits have not yet been confirmed in human HFpEF patients. Likewise, King’s College London cautioned against interpreting the findings as support for using pomegranates to 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 future HFpEF research and demonstrates how urolithin A activates this pathway in experimental systems. HFpEF remains a prevalent form of heart failure, often occurring alongside conditions such as high blood pressure, obesity, and diabetes. The findings provide molecular insights into how heart relaxation might be influenced via this mechanism. Nevertheless, clinical trials involving patients are necessary to establish whether urolithin A can safely produce similar effects in those with HFpEF.