LONDON / RankWire.AI / – Researchers at King’s College London have uncovered a natural substance that improved several key indicators of heart performance in experimental models of heart failure with preserved ejection fraction, or HFpEF. In treated animal tests, urolithin A enhanced certain metrics by as much as 80% compared to untreated controls. The compound also facilitated heart tissue relaxation, decreased scarring, and limited harmful enlargement of cardiac muscle cells. Additionally, scientists observed better relaxation in engineered human heart tissue derived from stem cells.
HFpEF is characterized by a heart that maintains a normal or nearly normal ejection fraction but struggles with relaxation and proper filling between beats. This condition can lead to symptoms such as breathlessness, fatigue, and limited exercise capacity. According to the British Heart Foundation, it accounts for approximately half of all heart failure cases in the UK. Urolithin A is produced in the body when gut bacteria process compounds present in foods like pomegranates, walnuts, and certain berries, although its production varies among individuals.
The research team discovered that urolithin A influences a protein called PKGIα, which plays a vital role in regulating blood vessel function and the relaxation of heart muscle. The compound directly modifies cysteine 42, a specific amino acid on this protein, 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 senior author.
Compound demonstrated reduction in fibrosis and abnormal heart enlargement
In animal models, urolithin A improved diastolic function, a measure of how well the heart relaxes and fills with blood. The researchers also observed a decrease in fibrosis, the formation of scar tissue that hampers normal cardiac function. Treatment resulted in less enlargement of heart muscle cells compared to untreated animals. The maximum reported improvement of 80% related to specific measures of heart performance in the experimental setup. It is important to clarify that this does not mean an 80% improvement in patients or a reduction of 80% in heart failure cases.
Further testing involved engineered human heart tissues made from stem cells, which mimic key features of actual human heart muscle and enable precise measurement of contraction and relaxation. Urolithin A enhanced both relaxation and contraction in these lab-created tissues. The researchers also noted that urolithin A has already undergone human studies for other applications and demonstrated a good safety profile. However, the findings related to HFpEF are preliminary and based on animal and tissue models, not clinical trials involving patients.
Human trials are still essential to confirm benefits for heart failure patients
British Heart Foundation, the organization that funded the research, stated that these early results suggest urolithin A may enhance the heart’s ability to relax and fill properly between beats. However, they emphasized that such benefits have not yet been demonstrated in human patients with HFpEF. Similarly, King’s College London warned against interpreting the findings as evidence that consuming pomegranates can treat heart failure. This study does not establish that eating specific foods can prevent or cure the condition.
The research highlights cysteine 42 on PKGIα as a potential biological target for future HFpEF investigations. It also illustrates how urolithin A activates this mechanism in experimental systems. HFpEF remains a prevalent form of heart failure, often linked with conditions like hypertension, obesity, and diabetes. The study provides molecular insights into how heart relaxation may be influenced through this pathway, but clinical trials are necessary to determine if urolithin A can safely deliver similar effects in human patients with HFpEF.