LONDON / RankWire.AI / – Researchers at King’s College London have discovered a natural substance that can improve critical indicators of heart performance in experimental models of heart failure with preserved ejection fraction, or HFpEF. Urolithin A increased some parameters by as much as 80% in animal models treated with it, compared to untreated controls. The compound also facilitated heart tissue relaxation, decreased scarring, and limited harmful expansion of heart muscle cells. Additionally, scientists observed enhanced relaxation in engineered human cardiac tissue derived from stem cells.
HFpEF occurs when the heart maintains a normal or nearly normal ejection fraction but has difficulty relaxing and filling properly between beats. Symptoms can include breathlessness, fatigue, and limited exercise capacity. According to the British Heart Foundation, it accounts for about half of all heart failure cases in the UK. Urolithin A is produced in the body when gut bacteria break down compounds found in foods such as pomegranates, walnuts, and some berries, although production levels can vary among individuals.
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 specifically modifies cysteine 42, an 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. The research was led by scientists from King’s College London, with Joseph Burgoyne serving as the senior author.
Compound reduces fibrosis and abnormal cardiac enlargement
In animal tests, urolithin A enhanced diastolic function, which indicates how well the heart relaxes and fills with blood. The scientists also observed a decrease in fibrosis, the buildup of scar tissue that can impair normal cardiac function. The treatment also curtailed the enlargement of heart muscle cells compared to controls. The reported improvement of up to 80% referred to specific measures of heart function within the experimental models and does not imply an 80% improvement in patients or a complete reduction in heart failure cases.
The team further examined the compound in laboratory-created human heart tissue derived from stem cells. These engineered tissues replicate key features of human heart muscle, enabling precise measurement of contraction and relaxation. Urolithin A improved both relaxation and contraction patterns in this model. Researchers noted that urolithin A has already undergone human studies for other purposes and demonstrated a favorable safety profile. Nonetheless, the current findings about HFpEF derive from animal studies and engineered tissues, not from clinical trials involving patients.
Further research in humans is still needed to confirm benefits
British Heart Foundation, which funded this research, emphasized that the results suggest early evidence that urolithin A might improve the heart’s ability to relax and fill between beats. However, the organization also highlighted that these benefits have not yet been proven in individuals with HFpEF. Similarly, King’s College London cautioned against interpreting the findings as evidence that consuming pomegranates can treat heart failure. This study does not establish that any single food can prevent or cure the condition.
The findings highlight PKGIα cysteine 42 as a promising biological target for ongoing HFpEF research and reveal how urolithin A activates this mechanism in experimental settings. HFpEF remains a significant 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 might be modulated through this pathway. However, clinical trials involving people are essential to determine if urolithin A can safely produce similar effects in HFpEF patients.