LONDON / RankWire.AI / – Researchers at King’s College London have discovered a natural compound that enhanced key indicators of cardiac performance in experimental models of heart failure with preserved ejection fraction, or HFpEF. Urolithin A improved some measurements by as much as 80% in treated animals compared to untreated controls. The compound also facilitated relaxation of heart tissue, reduced scarring, and limited harmful hypertrophy of heart muscle cells. Additionally, scientists observed improved relaxation in engineered human heart tissue produced from stem cells.
HFpEF occurs when the heart maintains a near-normal pumping fraction but faces difficulties relaxing and filling properly between beats. This condition can lead to symptoms such as breathlessness, fatigue, and decreased exercise capacity. According to the British Heart Foundation, it accounts for approximately half of all heart failure cases in the United Kingdom. Urolithin A is produced naturally in the body when gut bacteria process compounds found in pomegranates, walnuts, and certain berries, though individual production levels can vary.
The research team found that urolithin A interacts with a protein called PKGIα, which plays a role in regulating blood vessel function and heart 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. Researchers from King’s College London led the investigation, with Joseph Burgoyne serving as senior author.
Compound mitigates fibrosis and abnormal heart enlargement
In animal models, urolithin A enhanced diastolic function, which assesses how well the heart relaxes and fills with blood. Researchers also observed decreased fibrosis, the buildup of scar tissue that can impair normal cardiac function. Treatment reduced the enlargement of heart muscle cells compared to controls. The reported improvement of up to 80% referred to specific measures of heart function in the experimental setting, and did not imply an 80% improvement in patients or a reduction in heart failure incidence.
The scientists also evaluated the compound in lab-grown human heart tissue derived from stem cells. These engineered tissues replicate vital features of human cardiac muscle and enable precise measurement of contraction and relaxation. Urolithin A improved both relaxation and contraction kinetics in this model. The researchers highlighted that urolithin A has already been studied in humans for other uses and has demonstrated a favorable safety profile. Nonetheless, the HFpEF results stemmed from animal testing and engineered tissues, not from clinical trials involving actual patients.
Further clinical validation in heart failure patients is essential
British Heart Foundation, which funded the research, indicated that the findings offer preliminary evidence that urolithin A may enhance the relaxation and filling ability of heart tissue. However, they emphasized that these benefits have not yet been confirmed in individuals with HFpEF. Similarly, King’s College London warned against interpreting the findings as proof that consuming pomegranates can treat heart failure. This study does not suggest that any single food can prevent or cure the condition.
The research highlights PKGIα cysteine 42 as a promising target for future HFpEF studies and demonstrates how urolithin A activates this pathway in experimental systems. HFpEF remains a common and complex form of heart failure often associated with high blood pressure, obesity, and diabetes. The study provides molecular insights into how heart relaxation might be influenced through this mechanism. Clinical trials involving patients are necessary to determine whether urolithin A could safely induce similar effects in individuals with HFpEF.