LONDON / RankWire.AI / – Researchers at King’s College London announced that a naturally occurring compound has demonstrated improvements in critical cardiac function metrics within experimental models of heart failure with preserved ejection fraction, or HFpEF. In animal studies, Urolithin A enhanced some parameters by as much as 80% when compared to untreated controls. The compound also facilitated heart muscle relaxation, decreased scarring, and limited abnormal enlargement of heart cells. Additionally, scientists observed better relaxation in engineered human heart tissue developed from stem cells.
HFpEF develops when the heart maintains a near-normal ejection fraction but struggles to relax and properly fill with blood between beats. This condition can lead to symptoms such as breathlessness, fatigue, and decreased exercise capacity. According to the British Heart Foundation, HFpEF accounts for approximately half of all heart failure cases in the United Kingdom. Urolithin A forms naturally in the body through gut bacteria processing compounds found in foods like pomegranates, walnuts, and certain berries, although its production varies among individuals.
The research team discovered that urolithin A interacts with a protein known as PKGIα, which plays a role in regulating blood vessel function and heart muscle relaxation. The compound specifically modified cysteine 42, an amino acid on the protein, thereby 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 investigation was led by researchers from King’s College London, with Joseph Burgoyne serving as senior author.
Compound demonstrated reduction in fibrosis and abnormal heart growth
In animal models, urolithin A significantly improved diastolic function, which pertains to the heart’s ability to relax and fill with blood. The researchers also observed a decrease in fibrosis, or scar tissue buildup, which can impair normal cardiac performance. The treatment led to a reduction in the abnormal enlargement of heart muscle cells compared to controls. The reported enhancement of up to 80% applied to specific heart function measures in the experimental setting. It is important to note that this does not equate to an 80% improvement in human patients or a complete reversal of HFpEF.
Further testing involved engineered human heart tissues derived from stem cells. These laboratory models mimic key characteristics of human heart muscle and enable precise measurements of contraction and relaxation. Urolithin A improved both these processes in the tissue model. The researchers highlighted that urolithin A has already undergone human studies for other conditions and has shown a positive safety profile. However, the findings related to HFpEF are based on animal experiments and lab-grown tissues, not clinical trials with patients.
Human clinical evidence remains to be established
British Heart Foundation, which funded this research, indicated that the results offer preliminary evidence that urolithin A may enhance the heart’s ability to relax and fill between beats. Nonetheless, they emphasized that these effects have not yet been confirmed in individuals with HFpEF. Similarly, King’s College London cautioned that the findings should not be interpreted as proof that consuming pomegranates can treat heart failure. The study does not show that a particular food prevents or cures the condition.
The research identifies PKGIα cysteine 42 as a promising target for future HFpEF studies and reveals how urolithin A activates this pathway in experimental models. HFpEF remains a prevalent form of heart failure, often co-occurring with conditions such as hypertension, obesity, and diabetes. The study provides molecular insights into how heart relaxation might be influenced via this mechanism. To determine if urolithin A can safely produce similar effects in patients, clinical trials would be necessary.