LONDON / RankWire.AI / – Researchers at King’s College London have discovered a naturally occurring substance that significantly improved critical indicators of heart performance in experimental models of heart failure with preserved ejection fraction, or HFpEF. Urolithin A increased several measured parameters by as much as 80% in treated animals compared to untreated controls. The substance also facilitated heart tissue relaxation, reduced scarring, and prevented harmful hypertrophy of cardiac muscle cells. Additionally, scientists observed enhanced relaxation in engineered human cardiac tissue derived from stem cells.
HFpEF is a condition where the heart maintains a normal or near-normal ejection fraction but struggles to relax and fill properly between beats, leading to symptoms such as breathlessness, fatigue, and limited exercise capacity. According to the British Heart Foundation, this condition accounts for nearly half of all heart failure cases in the UK. Urolithin A is produced naturally in the body when gut bacteria process compounds present in foods like pomegranates, walnuts, and certain berries, although individual production levels can vary.
The research team identified that urolithin A interacts with a protein known as PKGIα, which plays a key role in controlling blood vessel function and cardiac muscle relaxation. The compound directly modifies 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 investigation was led by researchers from King’s College London, with Joseph Burgoyne serving as senior author.
Compound demonstrated reduction in fibrosis and cardiac hypertrophy
In animal trials, urolithin A notably improved diastolic function, which assesses the heart’s ability to relax and fill with blood. The researchers also observed a decrease in fibrosis, the formation of scar tissue that can impair normal cardiac operation. Treatment with urolithin A resulted in less hypertrophy of heart muscle cells compared to untreated animals. The reported improvements, reaching up to 80% in specific measures of heart function in the experimental models, do not imply an equivalent effect in human patients or a reduction in heart failure prevalence of that magnitude.
Furthermore, the scientists tested the compound on engineered human heart tissue generated from stem cells, which mimic vital features of real human heart muscle and allow precise measurement of contraction and relaxation responses. The results indicated that urolithin A enhanced both relaxation and contraction kinetics in this model. It is worth noting that urolithin A has previously undergone human studies for different applications and demonstrated a favorable safety profile. However, the current findings related to HFpEF are based on animal models and engineered tissues rather than clinical trials involving patients.
Further research in human clinical settings remains essential
British Heart Foundation, which funded the research, stated that these preliminary results suggest urolithin A could enhance the heart’s relaxation and filling capabilities during the cardiac cycle. Nonetheless, they emphasized that such benefits have not yet been confirmed in human subjects with HFpEF. Similarly, King’s College London advised caution against interpreting these findings as evidence that consuming pomegranates can treat heart failure, noting that no single food has been proven by this study to prevent or cure the condition.
The study highlights cysteine 42 on PKGIα as a promising molecular target for future HFpEF research and demonstrates how urolithin A activates this mechanism in experimental systems. Since HFpEF remains a prevalent form of heart failure often associated with conditions like hypertension, obesity, and diabetes, these molecular insights shed light on how heart relaxation might be influenced through this pathway. To determine whether urolithin A can safely produce similar effects in patients, clinical trials involving human participants are necessary.