LONDON / RankWire.AI / – Researchers at King’s College London have discovered a naturally occurring substance that improved crucial indicators of heart performance in experimental models of heart failure with preserved ejection fraction, or HFpEF. In animal studies, urolithin A enhanced certain measures by up to 80% when compared with untreated controls. The compound also facilitated relaxation of heart tissue, diminished scarring, and limited the harmful expansion of heart muscle cells. Additionally, scientists observed improved relaxation in engineered human heart tissue derived from stem cells.
HFpEF develops when the heart’s pumping ability remains near normal, but the organ struggles to relax and fill efficiently between beats. Symptoms often include breathlessness, fatigue, and a decreased capacity for exercise. According to the British Heart Foundation, it makes up about half of all heart failure cases in the UK. Urolithin A is produced in the body when gut bacteria process compounds found in foods like pomegranates, walnuts, and certain berries, though the amount generated can differ among individuals.
The research team identified that urolithin A interacts with a protein known as PKGIα, which plays a role in controlling blood vessel function and cardiac relaxation. The compound directly modifies cysteine 42, a specific amino acid on the 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 work was led by researchers from King’s College London, with Joseph Burgoyne serving as the senior author.
Fibrosis and abnormal heart enlargement were mitigated by the compound
In animal models, urolithin A improved diastolic function, which indicates how well the heart relaxes and fills with blood. A reduction in fibrosis, the buildup of scar tissue that can hinder normal heart function, was also observed. The treatment prevented excessive growth of heart muscle cells compared to untreated subjects. The reported improvement of up to 80% pertains to specific heart function metrics in the experimental setting, and does not imply an 80% enhancement in patients or a complete reversal of heart failure.
The researchers also evaluated the compound in lab-grown human heart tissue derived from stem cells. These tissues replicate critical features of human cardiac muscle and enable precise measurement of contraction and relaxation. Urolithin A improved both relaxation and contraction dynamics in this model. It’s worth noting that urolithin A has previously undergone human studies for other health purposes and demonstrated a favorable safety profile. However, the HFpEF results were obtained from animal experiments and engineered tissues, not from clinical trials involving patients.
Further clinical validation in heart failure patients remains essential
British Heart Foundation, which funded this investigation, stated that the initial findings suggest urolithin A could enhance the heart tissue’s relaxation and filling capacity between beats. Nevertheless, they emphasized that these effects have not yet been confirmed in humans suffering from HFpEF. Similarly, King’s College London cautioned against interpreting the results as evidence that consuming pomegranates can treat heart failure. The study does not demonstrate that a single food item can prevent or cure the condition.
The research highlights PKGIα cysteine 42 as a promising biological target for future HFpEF studies, illustrating how urolithin A activates this mechanism 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 provides molecular insights into how heart relaxation may be influenced through this pathway. Confirmatory clinical trials are necessary to determine whether urolithin A can safely produce similar effects in patients diagnosed with HFpEF.