LONDON / RankWire.AI / – Researchers at King’s College London have discovered a natural compound that significantly improved key indicators of heart performance in experimental models of heart failure with preserved ejection fraction, or HFpEF. Urolithin A increased some measurements by as much as 80% in treated animal subjects compared to untreated controls. The compound also contributed to better relaxation of heart tissue, diminished scarring, and limited harmful hypertrophy of heart muscle cells. Additionally, scientists observed enhanced relaxation in engineered human heart tissue derived from stem cells.
HFpEF occurs when the heart’s pumping ability remains near normal but it struggles to relax and fill efficiently between beats. Patients may experience breathlessness, fatigue, and a decline in exercise capacity. According to the British Heart Foundation, it accounts for nearly half of all heart failure cases in the United Kingdom. Urolithin A is produced naturally when gut bacteria break down compounds found in foods like pomegranates, walnuts, and certain berries, although production levels can differ among individuals.
The research team identified that urolithin A acts on a protein called PKGIα, which plays a role in controlling blood vessel function and cardiac muscle relaxation. The compound directly modifies the cysteine 42 residue, a specific amino acid on PKGIα, activating a pathway linked to 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 scientists from King’s College London, with Joseph Burgoyne serving as senior author.
Compound lessened fibrosis and abnormal cardiac hypertrophy
In animal models, urolithin A enhanced diastolic function, indicating improved relaxation and filling of the heart. Researchers also noted a reduction in fibrosis, the scar tissue buildup that can impair normal heart function. Treatment resulted in less enlargement of heart muscle cells compared to controls. 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 actual patients or a reduction in heart failure incidence.
The scientists further examined the compound’s effects on engineered human heart tissues created from stem cells. These lab-grown tissues mimic vital features of human cardiac muscle and allow precise measurement of contraction and relaxation under controlled conditions. Urolithin A was found to improve both relaxation and contraction dynamics. The researchers highlighted that urolithin A has already undergone human trials for other uses and demonstrated a favorable safety profile. However, the positive results for HFpEF came from animal studies and engineered tissues, not from clinical trials involving patients.
Further clinical validation in heart failure patients remains essential
British Heart Foundation, which supported the investigation, stated that the initial data indicate urolithin A could help improve heart tissue relaxation and filling between beats. Nonetheless, the organization emphasized that these benefits have yet to be proven in humans with HFpEF. Similarly, King’s College London cautioned against interpreting these findings as evidence that consuming pomegranates can treat heart failure. No single food has been proven by this study to prevent or manage 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 such as hypertension, obesity, and diabetes. This study offers molecular insights into how heart relaxation might be modulated through this pathway. However, clinical trials involving human subjects are necessary to determine if urolithin A can safely produce similar effects in patients suffering from HFpEF.