Low Blood Levels of EPA Linked to Heart Failure with Preserved Pumping Function in Mouse and Human Studies

This research looked at heart failure with preserved ejection fraction (HFpEF), a common type of heart failure where the heart’s pumping ability looks normal but it doesn’t relax and fill properly. Scientists measured blood fats in people with this condition and found that lower levels of eicosapentaenoic acid (EPA), an omega-3 fatty acid, tracked with more severe stiffness and filling problems in the heart.

To understand why, researchers used a mouse model that combines a high-fat diet with a drug that mimics some human heart failure features. Mice given high doses of EPA (equivalent to about 2-4 grams per day in humans) showed less heart cell death and improvements in heart relaxation and filling, both when EPA was given ahead of time and after problems had developed.

The team traced this effect to a protein called TREM2, found on immune cells, which helps clear away damaged or dying cells (a process called efferocytosis). EPA appeared to boost the amount of working TREM2 on cell surfaces while reducing the breakdown of this protein into an inactive fragment. When researchers removed TREM2 entirely in mice, EPA’s benefits on heart function and cell clearance disappeared, confirming that TREM2 was central to how EPA worked in this model.