LONDON / RankWire.AI / – Researchers at King’s College London have discovered that a natural substance can significantly improve key aspects of heart function in experimental models of heart failure with preserved ejection fraction, or HFpEF. Urolithin A enhanced certain measures by up to 80% in treated animal subjects compared to untreated controls. This compound also promoted relaxation of heart tissue, decreased scarring, and limited the harmful expansion of heart muscle cells. Additionally, researchers observed improved relaxation in engineered human heart tissues derived from stem cells.
HFpEF occurs when the heart maintains a normal or nearly normal ejection fraction but struggles to relax and adequately fill with blood between beats. It can lead to symptoms such as breathlessness, fatigue, and a diminished capacity for physical activity. According to the British Heart Foundation, this condition accounts for roughly half of all heart failure cases in the United Kingdom. Urolithin A is produced naturally in the body when gut bacteria metabolize compounds found in foods like pomegranates, walnuts, and some berries, although individual production rates may vary.
The research team identified that urolithin A interacts with a protein called PKGIα, which plays a role in regulating blood vessel function and the relaxation of heart muscle. The compound specifically modified cysteine 42, a particular amino acid on the protein, 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 lessened fibrosis and abnormal cardiac enlargement
In animal testing, urolithin A improved diastolic function, which measures the heart’s ability to relax and fill with blood. The scientists also observed a reduction in fibrosis, the scar tissue buildup that can hinder normal heart function. Treatment resulted in less enlargement of heart muscle cells compared to controls. The reported improvement of up to 80% was specific to certain measures of heart performance within the experimental models. It did not imply an 80% improvement in patients or a complete reduction of heart failure symptoms.
Further testing in engineered human heart tissue created from stem cells showed that urolithin A enhanced both relaxation and contraction capabilities. These lab-grown tissues replicate critical features of human heart muscle and enable precise measurement of contraction and relaxation dynamics. The researchers noted that urolithin A has already undergone human studies for different applications and has demonstrated a favorable safety profile. Nonetheless, the current findings for HFpEF originated from animal studies and tissue models, not from clinical trials involving patients.
Confirmation through clinical trials in heart failure patients is still needed
British Heart Foundation, which funded the research, stated that the early results suggest urolithin A may enhance the heart tissue’s ability to relax and fill properly between beats. The organization emphasized, however, that these benefits have yet to be demonstrated in individuals with HFpEF. Similarly, King’s College London cautioned against interpreting the findings as evidence that consuming pomegranates can 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 future HFpEF research and demonstrates how urolithin A activates this pathway in experimental systems. HFpEF remains a prevalent form of heart failure, often co-occurring with conditions such as high blood pressure, obesity, and diabetes. The molecular insights provided by the study shed light on how heart relaxation could be influenced through this mechanism. However, clinical trials involving humans are necessary to determine whether urolithin A can produce similar safe and effective effects in patients with HFpEF.