LONDON / RankWire.AI / – Researchers at King’s College London have discovered a natural compound that improves key indicators of cardiac performance in experimental models of heart failure with preserved ejection fraction, or HFpEF. Urolithin A increased some measures by as much as 80% in treated animals compared to untreated controls, and it also facilitated heart tissue relaxation, diminished scarring, and limited harmful hypertrophy of heart muscle cells. The team observed improved relaxation in engineered human heart tissues derived from stem cells as well.
HFpEF occurs when the heart maintains a near-normal or normal ejection fraction but struggles to relax and fill adequately between beats. Symptoms such as breathlessness, fatigue, and decreased exercise capacity often result. According to the British Heart Foundation, it accounts for about half of all heart failure cases in the UK. Urolithin A forms naturally in the body when gut bacteria metabolize compounds from foods like pomegranates, walnuts, and some berries, although its production varies between individuals.
The research indicated that urolithin A interacts with a protein called PKGIα, which plays a role in controlling blood vessel function and cardiac relaxation. The compound directly modifies cysteine 42, a specific amino acid residue 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 work was led by researchers from King’s College London, with Joseph Burgoyne serving as senior author.
Compound decreased fibrosis and abnormal hypertrophy
In animal experiments, urolithin A enhanced diastolic function, which assesses the heart’s ability to relax and fill with blood. The researchers also documented a reduction in fibrosis, the formation of scar tissue that hampers normal cardiac function. Treatment also lessened hypertrophy of heart muscle cells compared to controls. The observed improvements, up to 80% in specific heart function measures, do not imply an equivalent benefit or reduction in heart failure risk in human patients.
Further testing in engineered human cardiac tissue derived from stem cells showed that urolithin A improved both relaxation and contraction dynamics. These laboratory tissues mimic crucial features of human myocardium, allowing precise measurement of cardiac mechanics. The researchers highlighted that urolithin A has already been evaluated in human studies for other conditions and demonstrated a good safety profile. Nonetheless, the findings related to HFpEF stem from animal models and engineered tissues, not clinical trials involving patients.
Human clinical validation remains essential
British Heart Foundation, which funded the research, noted that these early results suggest urolithin A could enhance the heart’s ability to relax and fill between beats. However, they emphasized that these benefits have yet to be demonstrated in individuals with HFpEF. Similarly, King’s College London warned against interpreting the findings as evidence that consuming pomegranates could treat heart failure, as no single food has been proven to prevent or cure this condition based on this study.
The research highlights PKGIα cysteine 42 as a potential target for future HFpEF studies and demonstrates how urolithin A activates this pathway in experimental systems. Since HFpEF often co-occurs with conditions like high blood pressure, obesity, and diabetes, understanding how heart relaxation can be influenced through this mechanism is crucial. Ultimately, clinical trials involving humans are necessary to determine if urolithin A can safely produce similar effects in patients with HFpEF.