LONDON / RankWire.AI / – Researchers at King’s College London have discovered a natural substance that significantly improved key indicators of heart function in experimental models of heart failure with preserved ejection fraction, or HFpEF. Urolithin A enhanced some of these measures by as much as 80% in treated animal subjects compared to untreated controls. Additionally, the compound aided in relaxing heart tissue, decreased scarring, and limited abnormal growth of heart muscle cells. Scientists also observed improved relaxation responses in engineered human heart tissues derived from stem cells.
HFpEF occurs when the heart’s pumping ability remains close to normal, but its ability to relax and fill properly between beats is impaired. This condition can lead to symptoms such as breathlessness, fatigue, and reduced capacity for physical activity. According to the British Heart Foundation, it makes up roughly half of all heart failure cases in the UK. Urolithin A is produced in the body when gut bacteria process compounds found in foods like pomegranates, walnuts, and certain berries, though production levels can differ 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 directly modifies cysteine 42, a specific amino acid on the protein, thereby activating a pathway associated with cardiovascular health. The study was published in Science Advances under the title “Targeting PKGIα Cys42 attenuates cardiac dysfunction in heart failure with preserved ejection fraction.” The work was led by researchers from King’s College London, with Joseph Burgoyne serving as senior author.
Compound decreased fibrosis and prevented abnormal heart enlargement
In animal experiments, urolithin A notably improved diastolic function, which measures the heart’s ability to relax and fill with blood. The scientists also documented a reduction in fibrosis, which is the accumulation of scar tissue that hampers normal cardiac performance. The treatment also lessened the expansion of heart muscle cells compared to untreated controls. The reported 80% improvement pertained to specific heart function parameters in the animal model, not in human patients, nor did it signify an 80% reduction in heart failure incidence.
The researchers further tested the compound on engineered human heart tissue derived from stem cells. These lab-grown tissues replicate critical aspects of human heart muscle, enabling precise assessment of contraction and relaxation under controlled conditions. Urolithin A enhanced both relaxation and contraction dynamics in this model. It is noteworthy that urolithin A has previously undergone human studies for other health purposes and demonstrated a favorable safety profile. However, the findings related to HFpEF are currently based on animal data and engineered tissue, not clinical trials involving human patients.
Further clinical research in heart failure patients is essential
British Heart Foundation, which funded this investigation, indicated that these early results suggest urolithin A has the potential to improve heart tissue relaxation and filling between beats. Nonetheless, the organization emphasized that such benefits have yet to be demonstrated in humans suffering from HFpEF. Similarly, King’s College London advised against interpreting these findings as evidence that consuming pomegranates can treat heart failure. No individual food has been proven by this study to prevent or cure the condition.
The research highlights PKGIα cysteine 42 as a promising biological target for ongoing HFpEF studies and illustrates how urolithin A activates this mechanism in experimental systems. HFpEF remains a prevalent form of heart failure, often co-occurring with conditions like hypertension, obesity, and diabetes. The study provides molecular insights into how heart relaxation might be influenced through this pathway. To determine whether urolithin A can safely produce similar effects in patients with HFpEF, clinical trials involving humans would be necessary.