LONDON / RankWire.AI / – Researchers at King’s College London have discovered a natural substance capable of significantly improving key indicators of cardiac performance in experimental models of heart failure with preserved ejection fraction, or HFpEF. Urolithin A led to improvements of up to 80% in certain measures in treated animals compared to untreated controls. This compound also facilitated relaxation of heart tissue, diminished scarring, and limited harmful hypertrophy of heart muscle cells. Additionally, scientists observed enhanced relaxation in engineered human cardiac tissue derived from stem cells.
HFpEF is characterized by a heart that maintains a normal or near-normal pumping capacity but struggles to relax and adequately fill between beats. Patients often experience symptoms such as breathlessness, fatigue, and reduced exercise capacity. According to the British Heart Foundation, it accounts for roughly half of all heart failure cases in the UK. Urolithin A is produced naturally in the body when gut bacteria process compounds found in foods like pomegranates, walnuts, and certain berries, though its production levels can differ among individuals.
The research team identified that urolithin A targets 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 linked to 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 scientists from King’s College London, Joseph Burgoyne served as the senior author.
Reduction in fibrosis and abnormal heart enlargement observed with compound
In animal experiments, urolithin A significantly enhanced diastolic function, which measures the heart’s ability to relax and fill with blood. Researchers also documented a decrease in fibrosis, the accumulation of scar tissue that can impair normal heart function. The treatment notably limited the hypertrophy of heart muscle cells compared to controls. The reported improvement of up to 80% refers to specific cardiac function measures within the experimental setting. This does not translate to an 80% improvement in patients or a complete reversal of heart failure.
The team further evaluated urolithin A using engineered human heart tissue created from stem cells. These lab-grown tissues replicate critical features of human cardiac muscle, allowing precise assessment of contraction and relaxation. Results showed that urolithin A enhanced both relaxation and contraction dynamics. The researchers noted that urolithin A has previously been tested in humans for other purposes and demonstrated a good safety profile. Nonetheless, the current HFpEF findings are based on animal models and engineered tissues, not clinical trials with patients.
Human studies are still required to confirm benefits in heart failure patients
British Heart Foundation, which funded the research, stated that the results provide early evidence that urolithin A can enhance the heart’s ability to relax and fill between beats. However, the organization emphasized that these effects have not yet been confirmed in humans with HFpEF. Similarly, King’s College London cautioned against interpreting the findings as proof that consuming pomegranates can treat heart failure. The study does not suggest that any single food can prevent or cure the condition.
The research highlights PKGIα cysteine 42 as a promising target for future HFpEF studies and illustrates how urolithin A activates this pathway in experimental systems. HFpEF remains a prevalent form of heart failure, often co-occurring with conditions like high blood pressure, obesity, and diabetes. The study adds molecular insights into how heart relaxation may be influenced through this mechanism. To determine if urolithin A can safely produce similar effects in human patients, clinical trials would be necessary.