LONDON / RankWire.AI / – Researchers at King’s College London have discovered a natural substance that improved several key indicators of heart function in experimental models of heart failure with preserved ejection fraction, or HFpEF. Urolithin A increased some measures by as much as 80% in treated animal models compared to untreated controls. The compound also facilitated relaxation of heart tissue, decreased scarring, and limited harmful enlargement of cardiac muscle cells. In addition, scientists observed better relaxation in engineered human heart tissue derived from stem cells.
HFpEF occurs when the heart maintains a normal or near-normal pumping fraction but faces difficulty relaxing and filling properly between beats. This condition can cause symptoms like breathlessness, fatigue, and reduced capacity for exercise. 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 in the body when gut bacteria process compounds found in foods such as pomegranates, walnuts, and some berries. However, individual production levels can vary significantly.
The research team identified that urolithin A targets a protein called PKGIα, which plays a role in regulating blood vessel function and cardiac muscle relaxation. The compound directly modifies cysteine 42, a specific amino acid on this 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 Lessens Fibrosis and Abnormal Cardiac Enlargement
In animal models, urolithin A improved diastolic function, which measures how effectively the heart relaxes and fills with blood. The researchers also documented a reduction in fibrosis, which is the buildup of scar tissue that can disrupt normal cardiac performance. The treatment also decreased the enlargement of heart muscle cells compared to controls. The reported improvement of up to 80% applied specifically to certain heart function measures in the experimental setting. It does not mean an 80% improvement in patients or an 80% reduction in heart failure cases.
Furthermore, the team tested urolithin A in engineered human heart tissue created from stem cells. These laboratory tissues replicate important features of human cardiac muscle, allowing measurement of contraction and relaxation under controlled conditions. The compound enhanced both relaxation and contraction kinetics in this model. The researchers noted that urolithin A has already undergone studies in humans for other purposes and demonstrated a favorable safety profile. However, the positive findings for HFpEF were derived from animal studies and engineered tissues, not clinical trials with patients.
Human Clinical Evidence Still Needed to Confirm Benefits
British Heart Foundation, which funded the research, emphasized that the early results suggest urolithin A could improve the heart’s ability to relax and fill between beats. Nonetheless, they also stressed that these benefits have not yet been demonstrated in people with HFpEF. Similarly, King’s College London warned against interpreting these findings as evidence that consuming pomegranates can treat heart failure. This study does not show that a specific food can prevent or cure the condition.
The study highlights PKGIα cysteine 42 as a promising target for future HFpEF research. It also demonstrates how urolithin A activates this pathway in experimental systems. HFpEF remains a significant form of heart failure, often occurring alongside conditions like high blood pressure, obesity, and diabetes. This molecular insight advances understanding of how heart relaxation may be influenced through this mechanism. To determine if urolithin A can safely produce similar effects in patients, clinical trials would be essential.