LONDON / RankWire.AI / – Researchers at King’s College London have discovered a naturally occurring substance that enhanced critical indicators of cardiac performance in experimental models of heart failure with preserved ejection fraction, or HFpEF. In treated animal studies, urolithin A boosted several measures by up to 80% compared to untreated controls. The compound also promoted relaxation of heart tissue, decreased scarring, and limited harmful hypertrophy of heart muscle cells. Scientists further observed improved relaxation in engineered human heart tissue derived from stem cells.
HFpEF is characterized by the heart’s ability to pump blood normally or nearly normally, while struggling to relax and fill properly between beats. This condition can lead to symptoms such as breathlessness, fatigue, and reduced 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 certain berries, although individual production levels can vary.
The research team identified that urolithin A interacts with a protein called PKGIα, which plays a role in regulating blood vessel function and cardiac muscle relaxation. The compound directly modifies cysteine 42, a particular amino acid on the protein, and activates a pathway associated with cardiovascular health. The study, titled “Targeting PKGIα Cys42 attenuates cardiac dysfunction in heart failure with preserved ejection fraction,” was published by Science Advances. The research was led by scientists from King’s College London, with Joseph Burgoyne acting as senior author.
Compound decreased fibrosis and prevented abnormal heart enlargement
In animal tests, urolithin A enhanced diastolic function, which assesses the heart’s ability to relax and fill with blood. The researchers also observed a reduction in fibrosis, the accumulation of scar tissue that can impair normal cardiac function. Additionally, treatment limited the enlargement of heart muscle cells compared to untreated animals. The reported improvement of up to 80% pertained to specific measures of heart performance in the experimental setting, and did not imply an 80% improvement in human patients or a complete reversal of heart failure.
The scientists also evaluated the compound in engineered human heart tissue created from stem cells, which replicate essential features of human cardiac muscle and enable precise measurement of contraction and relaxation. Urolithin A improved both the relaxation and contraction processes in this model. Importantly, the researchers noted that urolithin A has previously undergone human studies for other purposes and demonstrated a favorable safety profile. Nonetheless, the HFpEF findings are based on animal models and engineered tissue, not yet confirmed in clinical trials with patients.
Further human research is essential to confirm clinical benefits
British Heart Foundation, which supported this investigation, stated that the initial results suggest urolithin A might improve the ability of heart tissue to relax and fill between beats. However, they emphasized that these effects have not yet been verified in individuals with HFpEF. Similarly, King’s College London warned against interpreting the findings as evidence that consuming pomegranates could treat heart failure. No single food has been proven by this research to prevent or cure the condition.
These findings highlight cysteine 42 on PKGIα as a potential molecular target for future HFpEF research and demonstrate how urolithin A activates this mechanism in experimental systems. HFpEF remains a significant subtype of heart failure, often occurring alongside conditions such as hypertension, obesity, and diabetes. The study provides molecular insights into how heart relaxation may be modulated through this pathway. However, clinical trials involving human participants are necessary to determine if urolithin A can safely replicate these effects in patients with HFpEF.