LONDON / RankWire.AI / – Researchers from King’s College London have uncovered a natural substance that boosts vital indicators of cardiac performance in experimental models of heart failure with preserved ejection fraction, or HFpEF. Urolithin A increased some parameters by as much as 80% in treated animals compared to untreated controls. This compound also facilitated relaxation of heart tissue, lessened scarring, and prevented harmful hypertrophy of cardiac muscle cells. The team additionally observed improved relaxation in engineered human heart tissue derived from stem cells.
HFpEF manifests when the heart maintains a near-normal pumping efficiency but faces difficulty relaxing and filling adequately between beats. Symptoms include breathlessness, fatigue, and diminished exercise capacity. According to the British Heart Foundation, it accounts for about half of all heart failure cases in the United Kingdom. Urolithin A is produced in the body when gut bacteria metabolize compounds present in foods like pomegranates, walnuts, and certain berries, although production levels differ among individuals.
The research team demonstrated that urolithin A targets a protein called PKGIα, which plays a key role in controlling blood vessel function and cardiac muscle relaxation. The compound directly modifies cysteine 42, a specific amino acid residue on the protein, thereby 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 acting as senior author.
Compound decreased fibrosis and prevented abnormal heart enlargement
In animal trials, urolithin A significantly improved diastolic function, which assesses the heart’s ability to relax and fill with blood. The researchers also observed a reduction in fibrosis, the formation of scar tissue that can impair normal cardiac function. Additionally, treatment curtailed the enlargement of heart muscle cells relative to controls. The reported maximum improvement of 80% pertained to specific measures of cardiac function within the experimental setting. This does not imply an 80% enhancement in patients or a reduction of 80% in heart failure incidence.
Further testing involved engineered human heart tissue created from stem cells, which mimic essential features of human cardiac muscle. These lab-grown tissues allowed precise measurement of contraction and relaxation responses. Urolithin A enhanced both relaxation and contraction kinetics in this model. Importantly, urolithin A has previously undergone human studies for other applications and demonstrated a favorable safety profile. Nonetheless, the findings related to HFpEF are derived from animal models and engineered tissues, not clinical trials involving patients.
Confirmation through clinical trials remains essential
British Heart Foundation, which funded this research, indicated that the results provide preliminary evidence that urolithin A can enhance the heart’s relaxation and filling phases. They also emphasized that these benefits have not yet been demonstrated in humans with HFpEF. Similarly, King’s College London warned against interpreting these findings as proof that consuming pomegranates can treat heart failure. No single food has been shown by this study to prevent or cure the condition.
The research highlights PKGIα cysteine 42 as a promising target for future HFpEF investigations and illustrates how urolithin A activates this pathway in experimental systems. HFpEF remains a prevalent form of heart failure, often co-occurring with hypertension, obesity, and diabetes. The study provides molecular insights into how heart relaxation may be modulated via this mechanism. To determine whether urolithin A can safely elicit similar effects in patients with HFpEF, clinical trials in humans are necessary.