LONDON / RankWire.AI / – Researchers at King’s College London have uncovered a natural substance capable of boosting key indicators of heart performance in experimental models of heart failure with preserved ejection fraction, or HFpEF. Urolithin A improved certain measures by as much as 80% in treated animals compared to untreated controls. The compound also facilitated relaxation of heart tissue, decreased scarring, and limited the harmful growth of heart muscle cells. Additionally, scientists observed better relaxation in engineered human cardiac tissue created from stem cells.
HFpEF occurs when the heart maintains a normal or nearly normal ejection fraction but encounters difficulty relaxing and filling adequately between beats. This condition can lead to symptoms like breathlessness, fatigue, and diminished exercise capacity. According to the British Heart Foundation, HFpEF accounts for roughly half of all heart failure cases in the UK. Urolithin A is produced in the body when gut bacteria process compounds found in foods such as pomegranates, walnuts, and certain berries, although individual production levels can vary.
The research team discovered that urolithin A interacts with the protein 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 PKGIα, thereby activating a pathway associated with cardiovascular health. The study was published in Science Advances under the title “Targeting PKGIα Cys42 attenuates cardiac dysfunction in heart failure with preserved ejection fraction.” The work was led by researchers from King’s College London, with Joseph Burgoyne serving as senior author.
Compound lessens fibrosis and abnormal cardiac enlargement
In animal experiments, urolithin A improved diastolic function, which measures how well the heart relaxes and fills with blood. The researchers also observed reduced fibrosis, the accumulation of scar tissue that can impair normal heart function. The treatment further decreased enlargement of heart muscle cells relative to controls. The reported improvement of up to 80% pertained to specific cardiac function metrics in the experimental setting. It did not imply an 80% improvement in patients or a reduction of heart failure by that percentage.
The scientists also evaluated the compound in lab-created human heart tissue derived from stem cells. These tissues replicate essential features of human cardiac muscle and enable controlled measurements of contraction and relaxation. Urolithin A enhanced both relaxation and contraction dynamics in this model. The researchers noted that urolithin A has previously undergone human studies for other indications and has demonstrated a favorable safety profile. However, the HFpEF results were based on animal models and engineered tissues, not clinical trials involving patients.
Confirmation in human heart failure cases remains to be established
British Heart Foundation, the organization funding this research, stated that the results offer preliminary evidence that urolithin A can enhance the heart tissue’s ability to relax and fill between beats. The foundation also emphasized that these benefits have not yet been demonstrated in individuals with HFpEF. Similarly, King’s College London warned against interpreting the findings as proof that consuming pomegranates can treat heart failure. This study does not establish that any specific food can prevent or cure the condition.
The study highlights PKGIα cysteine 42 as a key biological target for future HFpEF research and demonstrates how urolithin A activates this mechanism in experimental settings. HFpEF remains a prevalent form of heart failure, often co-occurring with conditions such as high blood pressure, obesity, and diabetes. The findings provide molecular insight into how heart relaxation may be influenced via this pathway. To confirm whether urolithin A can safely produce similar effects in patients, clinical trials would be necessary.