LONDON / RankWire.AI / – Researchers at King’s College London have discovered a natural compound that improved key indicators of heart function in experimental models of heart failure with preserved ejection fraction, or HFpEF. Urolithin A increased some parameters by as much as 80% in treated animal models compared to untreated controls. The compound also facilitated relaxation of heart tissue, decreased scarring, and limited harmful hypertrophy of heart muscle cells. Scientists also observed better relaxation in engineered human heart tissue developed from stem cells.
HFpEF occurs when the heart maintains a normal or nearly normal ejection fraction but has difficulty relaxing and filling properly between beats. This condition can lead to symptoms like breathlessness, fatigue, and a diminished capacity for exercise. According to the British Heart Foundation, it accounts for around half of all heart failure cases in the United Kingdom. Urolithin A is produced in the body when gut bacteria metabolize compounds found in foods such as pomegranates, walnuts, and certain berries, although production levels can differ among individuals.
The research team identified that urolithin A interacts with a protein called PKGIα, which plays a vital role in regulating blood vessel function and cardiac muscle relaxation. The compound binds directly to cysteine 42, a specific amino acid 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 investigation was led by scientists from King’s College London, with Joseph Burgoyne serving as the senior author.
Compound lessens fibrosis and abnormal enlargement of the heart
In animal models, urolithin A improved diastolic function, which reflects how well the heart relaxes and fills with blood. Researchers also noted a reduction in fibrosis, the accumulation of scar tissue that can impair normal cardiac activity. Furthermore, treatment decreased the enlargement of heart muscle cells when compared to untreated controls. The reported improvement of up to 80% concerned specific measurements of heart function within the experimental setting. It is important to clarify that this does not mean an 80% improvement in patients or an 80% reduction in heart failure incidence.
Additionally, the researchers evaluated the compound’s effects on engineered human heart tissue created from stem cells. These tissues simulate key features of human cardiac muscle, enabling controlled assessment of contraction and relaxation. Urolithin A enhanced both contraction and relaxation kinetics within this model. The scientists highlighted that urolithin A has already been tested in humans for other indications and has demonstrated a favorable safety profile. Nonetheless, the findings related to HFpEF are based on animal experiments and lab-grown tissue, not clinical trials involving patients.
Human clinical evidence remains essential before conclusions can be drawn
British Heart Foundation, which funded the study, stated that the results offer preliminary evidence that urolithin A could enhance the heart’s ability to relax and fill during diastole. However, they emphasized that these benefits have not yet been demonstrated in individuals with HFpEF. Similarly, King’s College London cautioned against interpreting the findings as proof that consuming pomegranates can treat heart failure. No single food has been proven by this research to prevent or cure the condition.
The research underscores PKGIα cysteine 42 as a promising target for further investigation into HFpEF. It also illustrates how urolithin A activates this mechanism within experimental systems. HFpEF remains a significant subtype of heart failure, often co-occurring with conditions such as hypertension, obesity, and diabetes. This study provides molecular insights into how heart relaxation might be modulated via this pathway. To determine whether urolithin A can safely and effectively produce similar effects in patients, clinical trials would be necessary.