LONDON / RankWire.AI / – Researchers at King’s College London have discovered a naturally occurring substance that improved vital indicators of cardiac performance in experimental models of heart failure with preserved ejection fraction, or HFpEF. In animal studies, urolithin A enhanced certain measures by up to 80% compared to untreated controls. Additionally, the compound facilitated relaxation of heart tissue, diminished scarring, and limited harmful hypertrophy of heart muscle cells. The team also observed improved relaxation in engineered human heart tissue derived from stem cells.
HFpEF is characterized by the heart maintaining a near-normal or normal pumping fraction while struggling to relax and fill 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 when gut bacteria process compounds found in foods like pomegranates, walnuts, and some berries, though individual production levels can vary.
The research team identified 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 directly modifies cysteine 42, a specific 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. Led by researchers from King’s College London, Joseph Burgoyne served as the senior author.
Compound demonstrated reduction in fibrosis and abnormal heart enlargement
In animal models, urolithin A improved diastolic function, which indicates how effectively the heart relaxes and fills with blood. The study also reported decreased fibrosis, the formation of scar tissue that can impair normal cardiac function. Treatment resulted in less enlargement of heart muscle cells compared to untreated controls. The reported improvement of up to 80% applied specifically to certain measures of heart function within the experimental setting. This does not imply an 80% improvement in human patients or a complete reduction in heart failure symptoms.
Researchers also examined the effects of the compound on engineered human heart tissue created from stem cells. These lab-grown tissues mimic crucial features of human heart muscle and allow precise measurement of contraction and relaxation responses. Urolithin A enhanced both relaxation and contraction dynamics in this model. The team highlighted that urolithin A has already been studied in humans for other indications and has exhibited a favorable safety profile. However, the current HFpEF findings are based on animal and engineered tissue studies, not clinical trials involving patients.
Further research is needed to confirm benefits in clinical settings
British Heart Foundation, which funded the investigation, noted that the results provide early evidence that urolithin A may enhance the heart tissue’s ability to relax and fill between beats. Nonetheless, they emphasized that these effects have yet to be demonstrated in individuals with HFpEF. Similarly, King’s College London cautioned against interpreting these findings as evidence that consuming pomegranates can treat heart failure. No single food has been proven by this research to prevent or cure the condition.
The study highlights cysteine 42 on PKGIα as a biological target for ongoing HFpEF research and demonstrates how urolithin A activates this pathway in experimental systems. HFpEF remains a significant form of heart failure, often co-occurring with conditions like hypertension, obesity, and diabetes. The research provides molecular insights into how heart relaxation may be modulated through this pathway. Confirmatory clinical trials in humans are essential to determine if urolithin A can safely produce similar effects in HFpEF patients.