LONDON / RankWire.AI / – Researchers at King’s College London identified a naturally occurring substance that improved key indicators of cardiac performance in experimental models of heart failure with preserved ejection fraction, or HFpEF. Urolithin A enhanced certain measures by up to 80% in treated animals compared to untreated controls. Additionally, the compound facilitated heart tissue relaxation, decreased scarring, and limited harmful expansion of heart muscle cells. Researchers also observed improved relaxation in engineered human cardiac tissue derived from stem cells.
HFpEF is characterized by the heart maintaining a near-normal or normal pumping fraction but experiencing difficulty relaxing and filling properly between beats. Symptoms can include breathlessness, fatigue, and a reduced capacity for exercise. According to the British Heart Foundation, it accounts for about half of all heart failure cases in the United Kingdom. Urolithin A forms naturally in the body when gut bacteria process compounds found in foods such as pomegranates, walnuts, and some berries, although individual production levels can vary.
The research team discovered 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 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 demonstrated reduction in fibrosis and abnormal cardiac hypertrophy
In animal models, urolithin A improved diastolic function, which measures how well the heart relaxes and fills with blood. Researchers also noted a decrease in fibrosis, the buildup of scar tissue that can impair normal heart performance. The treatment also reduced the enlargement of heart muscle cells compared to controls. The reported improvement of up to 80% pertained to specific measures of heart function within the experimental setting. This does not imply an 80% improvement in human patients or an 80% reduction in heart failure cases.
The study further examined the compound in engineered human heart tissue created from stem cells, which mimic essential features of human cardiac muscle and permit precise measurement of contraction and relaxation. Urolithin A enhanced both relaxation and contraction kinetics in this model. Researchers noted that urolithin A has already undergone human studies for other indications and has demonstrated a favorable safety profile. However, the HFpEF results originated from animal experiments and lab-grown tissues, not clinical trials involving patients.
Human clinical validation remains essential
British Heart Foundation, which funded the research, stated that the initial findings suggest urolithin A might improve how heart tissue relaxes and fills between beats. The organization emphasized, however, that these benefits have not yet been confirmed in individuals with HFpEF. Similarly, King’s College London cautioned against interpreting the results as evidence that consuming pomegranates can treat heart failure. The study does not show that any single food can prevent or cure the condition.
The findings pinpoint PKGIα cysteine 42 as a promising biological target for future HFpEF research and illustrate how urolithin A activates this mechanism in laboratory systems. HFpEF remains a significant form of heart failure, often co-occurring with conditions like high blood pressure, obesity, and diabetes. The study provides molecular insights into how heart relaxation might be influenced through this pathway. Ultimately, clinical trials involving patients are necessary to determine whether urolithin A can produce similar effects safely in those affected by HFpEF.