LONDON / RankWire.AI / – Researchers at King’s College London have uncovered a natural compound that enhances critical indicators of heart performance in experimental models of heart failure with preserved ejection fraction, or HFpEF. Urolithin A increased several measures by as much as 80% in treated animal subjects compared to untreated controls. The compound also facilitated relaxation of heart tissue, diminished scarring, and limited harmful growth of heart muscle cells. Additionally, researchers observed improved relaxation responses in engineered human heart tissue derived from stem cells.
HFpEF develops when the heart maintains a normal or near-normal pumping fraction but has difficulty relaxing and filling properly between beats. Symptoms may include breathlessness, fatigue, and a 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 in the body when gut bacteria break down compounds found in foods such as pomegranates, walnuts, and certain berries, although its production can vary between individuals.
The research team discovered that urolithin A influences a protein known as PKGIα, which plays a role in regulating blood vessel function and heart muscle relaxation. The compound specifically modifies cysteine 42, an amino acid on the protein, 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 by Science Advances. Leading the research was a team from King’s College London, with Joseph Burgoyne serving as the senior author.
Compound decreased fibrosis and abnormal hypertrophy of the heart
In animal models, urolithin A significantly improved diastolic function, which assesses the heart’s ability to relax and fill with blood. Researchers also noted a reduction in fibrosis, the formation of scar tissue that can impair cardiac performance. The treatment also curtailed the enlargement of heart muscle cells compared to untreated animals. The reported improvement of up to 80% related to specific measures of heart function in the experimental setting; it does not imply an 80% enhancement in patients or a complete reversal of heart failure.
Furthermore, the team tested the compound using engineered human heart tissue derived from stem cells. These laboratory-grown tissues replicate key features of human cardiac muscle, allowing precise measurement of contraction and relaxation. Urolithin A was found to enhance both contraction and relaxation dynamics in this model. Researchers also highlighted that urolithin A has already been evaluated in human studies for other uses, demonstrating a favorable safety profile. However, these HFpEF results are preliminary, based on animal models and lab tissue, not clinical trials involving patients.
Human clinical validation remains essential
British Heart Foundation, the organization funding the research, indicated that the results provide early evidence that urolithin A can enhance the heart’s relaxation and filling ability between beats. Nonetheless, they emphasized that these benefits have not yet been demonstrated in individuals with HFpEF. Similarly, King’s College London warned against interpreting these findings as proof that consuming pomegranates can treat heart failure. This study does not suggest any single food can prevent or cure the condition.
The findings point to PKGIα cysteine 42 as a promising target for further investigation in HFpEF research, illustrating how urolithin A activates this pathway in experimental systems. HFpEF remains a prevalent form of heart failure, often co-occurring with high blood pressure, obesity, and diabetes. The study offers molecular insights into how heart relaxation may be influenced via this mechanism. To establish whether urolithin A can safely produce similar effects in patients, clinical trials involving humans are necessary.