LONDON / RankWire.AI / – Researchers at King’s College London have pinpointed a natural substance that enhances critical indicators of cardiac performance in experimental models of heart failure with preserved ejection fraction, or HFpEF. Urolithin A showed improvements of up to 80% in certain measures in treated animal subjects compared to untreated controls. Additionally, the compound facilitated relaxation of heart tissue, diminished scarring, and curbed harmful enlargement of heart muscle cells. Findings also included improved relaxation responses in engineered human cardiac tissue derived from stem cells.
HFpEF is characterized by the heart maintaining a normal or nearly normal pumping capacity but experiencing difficulty relaxing and filling properly between beats. Symptoms often include breathlessness, fatigue, and limited exercise capacity. According to the British Heart Foundation, it accounts for about half of all heart failure cases in the UK. Urolithin A is produced naturally in the body when gut bacteria metabolize compounds present in foods like pomegranates, walnuts, and certain berries, although production levels can vary among individuals.
The research team discovered that urolithin A interacts with a protein called PKGIα, which plays a role in regulating blood vessel function and cardiac 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. The research was led by scientists from King’s College London, with Joseph Burgoyne serving as senior author.
Reduction of fibrosis and abnormal heart enlargement observed
In the animal experiments, urolithin A was found to enhance diastolic function, which assesses how well the heart relaxes and fills with blood. There was also a notable decrease in fibrosis, the scar tissue buildup that can impair normal cardiac function. The treatment minimized the enlargement of heart muscle cells compared to controls. The reported improvement of up to 80% pertained to specific cardiac function parameters in the experimental setting; it did not indicate an 80% improvement in human patients or a complete reduction in heart failure symptoms.
Researchers extended their investigation to engineered human heart tissue formed from stem cells, which emulate key features of human cardiac muscle. These tissues enabled measurement of contraction and relaxation under tightly controlled conditions. Urolithin A improved both relaxation and contraction dynamics in this model. It is noteworthy that urolithin A has previously undergone human studies for different purposes and demonstrated a favorable safety profile. Nonetheless, the findings related to HFpEF were obtained from animal models and lab-grown tissue, not from clinical trials involving patients.
Human clinical validation remains essential
British Heart Foundation, which funded the research, indicated that the early results suggest urolithin A could enhance the heart’s relaxation and filling capabilities. However, they emphasized that these benefits have not yet been confirmed in individuals with HFpEF. Similarly, King’s College London warned against interpreting the findings as evidence that consuming pomegranates could treat heart failure. No single food has been proven by this study to prevent or cure the condition.
The study highlights PKGIα cysteine 42 as a promising target for further investigation into HFpEF. It also illustrates how urolithin A activates this pathway within experimental systems. HFpEF remains a prevalent form of heart failure, often associated with conditions such as hypertension, obesity, and diabetes. These molecular insights reveal potential mechanisms by which heart relaxation might be influenced through this pathway. To determine if urolithin A can safely exert similar effects in patients, clinical trials involving people are essential.