LONDON / RankWire.AI / – Researchers at King’s College London have identified a natural substance capable of significantly improving key indicators of heart performance in experimental models of heart failure with preserved ejection fraction, or HFpEF. Urolithin A enhanced certain metrics by up to 80% in treated animal models compared to untreated controls. Additionally, the compound promoted relaxation of heart tissue, decreased scarring, and limited the harmful enlargement of cardiac muscle cells. These findings were also observed in engineered human heart tissue derived from stem cells, where relaxation was notably improved.
HFpEF is characterized by the heart’s ability to pump blood normally or nearly so, while struggling to relax and fill properly between beats. Symptoms can include breathlessness, fatigue, and a diminished capacity for physical activity. According to the British Heart Foundation, it accounts for approximately half of all heart failure cases in the United Kingdom. Urolithin A is produced naturally when gut bacteria process compounds found in foods such as pomegranates, walnuts, and certain berries, although its production varies among individuals.
The research team discovered that urolithin A interacts with a protein called PKGIα, which plays a crucial role in blood vessel regulation and heart muscle relaxation. The compound directly modifies cysteine 42, a specific amino acid on the protein, leading to activation of a pathway associated with cardiovascular health. The study, titled “Targeting PKGIα Cys42 attenuates cardiac dysfunction in heart failure with preserved ejection fraction,” was published by Science Advances. Leading the investigation was a team from King’s College London, with Joseph Burgoyne serving as the senior author.
Compound lessens fibrosis and abnormal heart enlargement
In the animal experiments, urolithin A improved diastolic function, which measures how well the heart relaxes and fills with blood. The researchers also observed a reduction in fibrosis, which is the accumulation of scar tissue that can impair normal cardiac activity. Furthermore, treatment decreased the enlargement of heart muscle cells when compared to untreated animals. The reported up to 80% improvement referred to specific measures of cardiac function within the experimental model and does not imply an equivalent benefit or reduction in heart failure in humans.
The scientists also evaluated the compound using engineered human heart tissue created from stem cells, which emulate critical features of real human heart muscle. These tissues enabled precise assessment of contraction and relaxation responses. Urolithin A was found to enhance both relaxation and contraction kinetics in this model. Notably, urolithin A has already undergone human studies for other indications and demonstrated a favorable safety profile. However, the positive findings regarding HFpEF were limited to animal models and laboratory tissue, with no current clinical trial data in patients.
Human clinical trials remain essential to confirm benefits
British Heart Foundation, which funded this research, stated that the results provide preliminary evidence that urolithin A can improve the heart tissue’s ability to relax and fill during diastole. The organization also emphasized that these effects have not yet been demonstrated in individuals with HFpEF. Similarly, King’s College London warned against interpreting the findings as an endorsement that consuming pomegranates can treat heart failure. This study does not establish that any single food can prevent or cure the condition.
The research highlights PKGIα cysteine 42 as a promising target for future HFpEF investigations and demonstrates how urolithin A activates this pathway in experimental settings. HFpEF remains a prevalent form of heart failure, often occurring alongside 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 determine if urolithin A can safely replicate these effects in patients, clinical trials involving human participants are necessary.