LONDON / RankWire.AI / – Researchers at King’s College London have discovered a naturally occurring substance that improved critical measures of heart performance in experimental models of heart failure with preserved ejection fraction, or HFpEF. In animal studies, urolithin A enhanced some parameters by up to 80% compared to untreated controls. The compound also facilitated relaxation of heart tissue, lowered scarring, and limited the harmful enlargement of cardiac muscle cells. Additionally, scientists observed improved relaxation in engineered human heart tissue made from stem cells.
HFpEF happens when the heart maintains a normal or nearly normal ejection fraction but struggles to relax and fill properly between beats. This condition can lead to symptoms like breathlessness, fatigue, and a reduced capacity for exercise. According to the British Heart Foundation, it accounts for approximately half of heart failure cases in the United Kingdom. Urolithin A forms inside the body when gut bacteria process compounds found in foods such as pomegranates, walnuts, and certain berries, although its production can vary among individuals.
The research team discovered that urolithin A interacts with a protein called PKGIα, which plays a role in regulating blood vessel function and heart muscle relaxation. The compound directly modified cysteine 42, a specific amino acid on the protein, thereby activating a pathway linked to 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 senior author.
Compound reduced fibrosis and prevented abnormal heart enlargement
In the animal experiments, urolithin A improved diastolic function, which measures how well the heart relaxes and fills with blood. Researchers also noted less fibrosis, the accumulation of scar tissue that can impair normal cardiac function. Treatment resulted in a decrease in the enlargement of heart muscle cells compared with controls. The reported improvement of up to 80% pertained to specific heart function measures in the experimental models. This does not mean an 80% improvement in patients or an 80% reduction in heart failure cases.
The team also evaluated urolithin A in engineered human heart tissues created from stem cells. These lab-grown tissues replicate key features of human heart muscle and allow precise measurement of contraction and relaxation. The compound improved both relaxation and contraction kinetics in this model. Importantly, urolithin A has previously undergone human studies for different purposes and has demonstrated a favorable safety profile. However, the HFpEF findings are based on animal models and engineered tissue, not clinical trials involving patients.
Clinical validation in heart failure patients remains essential
British Heart Foundation, which sponsored the research, stated that the results provide early-stage evidence that urolithin A can enhance the heart’s ability to relax and fill between beats. The organization emphasized that these benefits have not yet been confirmed in individuals with HFpEF. Similarly, King’s College London warned against interpreting these findings as proof that eating pomegranates can treat heart failure. This study does not show that any single food can prevent or cure the condition.
The research highlights PKGIα cysteine 42 as a promising biological target for further HFpEF investigation. It also demonstrates how urolithin A activates this pathway in experimental systems. HFpEF remains a significant form of heart failure, often co-occurring with high blood pressure, obesity, and diabetes. This study offers molecular insights into how heart relaxation might be influenced through this mechanism. Nevertheless, clinical trials involving humans are necessary to determine if urolithin A can safely produce similar effects in HFpEF patients.