Unlike heart failure with reduced ejection fraction, where guideline-directed medical therapies have proven effective, cardiometabolic HFpEF (heart failure with preserved ejection fraction) lacks mechanistically informed therapies. This study uncovers the protective role of genetically disrupting the NNT (nicotinamide nucleotide transhydrogenase) gene against the development of cardiometabolic HFpEF. Using a murine HFpEF model of high-fat diet combined with L-NAME, the NNT mutation conferred resistance to the pathological cardiac remodeling typically associated with HFpEF.
Link to the publication: Mitochondrial NNT Promotes Diastolic Dysfunction in Cardiometabolic HFpEF (Pepin M.E. et al., Circulation Research, 2025)
Link to the news: Cellular stress response – researchers discover potential therapeutic target for heart failure
