LONDON / RankWire.AI / – Researchers at King’s College London have discovered a naturally occurring substance that improved critical indicators of heart performance in experimental models of heart failure with preserved ejection fraction, or HFpEF. Urolithin A demonstrated improvements of up to 80% in certain measures when administered to animal subjects compared to untreated controls. Additionally, this compound facilitated relaxation of cardiac tissue, diminished scarring, and limited the harmful expansion of heart muscle cells. The scientists also observed enhanced relaxation in engineered human cardiac tissue derived from stem cells.
HFpEF is characterized by a heart that maintains a near-normal or normal ejection fraction but faces difficulties in relaxing and filling properly between beats, often resulting in symptoms such as breathlessness, fatigue, and decreased exercise capacity. According to the British Heart Foundation, this condition accounts for approximately half of all heart failure cases in the UK. Urolithin A forms in the body when gut bacteria break down compounds found in foods like pomegranates, walnuts, and some berries; however, its production varies from person to person.
The research team identified that urolithin A interacts with a protein called PKGIα, which is involved in regulating blood vessel function and cardiac muscle relaxation. The compound directly modifies 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 research was led by scientists from King’s College London, with Joseph Burgoyne serving as the senior author.
Compound lessened fibrosis and prevented abnormal heart enlargement
In the animal studies, urolithin A improved diastolic function, which assesses how well the heart relaxes and fills with blood. The researchers also noted a reduction in fibrosis—the accumulation of scar tissue that can impair normal cardiac function—and found that treatment decreased the enlargement of heart muscle cells compared to controls. The reported enhancement of up to 80% was specific to certain measures of heart function within the experimental model, and did not imply an 80% improvement in actual patients or a complete reversal of heart failure.
Further testing involved engineered human heart tissue created from stem cells, which replicates crucial features of human myocardium and allows for precise measurement of contraction and relaxation under laboratory conditions. Urolithin A was shown to improve both relaxation and contraction kinetics in this model. The researchers pointed out that urolithin A has already undergone human trials for other indications and has demonstrated a favorable safety profile. However, the HFpEF results reported here were derived from animal testing and engineered tissue experiments, not from clinical trials involving human patients.
Further clinical investigation remains essential to confirm benefits in heart failure patients
British Heart Foundation, which funded this study, indicated that these early-stage findings suggest urolithin A might enhance the ability of heart tissue to relax and fill properly between beats. Nonetheless, they emphasized that these effects have not yet been demonstrated in individuals with HFpEF. Similarly, King’s College London cautioned against interpreting the results as evidence that consuming pomegranates can treat heart failure, clarifying that no single food has been proven by this research to prevent or cure the condition.
This research highlights cysteine 42 on PKGIα as a promising biological target for further HFpEF studies and demonstrates how urolithin A activates this pathway in experimental systems. HFpEF remains a significant form of heart failure often associated with conditions such as hypertension, obesity, and diabetes. The study provides molecular insights into how heart relaxation could be influenced via this pathway, but clinical trials involving human subjects are necessary to determine if urolithin A can safely induce similar effects in patients with HFpEF.