NASH triggers cardiometabolic HFpEF in aging mice

• DOI: 10.1007/s11357-024-01153-9
• Publication Date: 2024-04-17T08:51:22Z
• Authors: Dániel Kucsera; Mihály Ruppert; Nabil V. Sayour; Viktória E. Tóth; Tamás Kovács; Zsombor I. Hegedűs; Zsófia Onódi; Alexandra Fábián; Attila Kovács; Tamás Radovits; Béla Merkely; Pál Pacher; Péter Ferdinandy; Zoltán V. Varga
• Keywords: Heart Failure; Male; Aging; Stroke Volume; Mice, Inbred C57BL; Disease Models, Animal; Mice; 03 medical and health sciences; 0302 clinical medicine; Non-alcoholic Fatty Liver Disease; Echocardiography; Animals; Original Article

Both heart failure with preserved ejection fraction (HFpEF) and non-alcoholic fatty liver disease (NAFLD) develop due to metabolic dysregulation, has similar risk factors (e.g., insulin resistance, systemic inflammation) are unresolved clinical challenges. Therefore, the potential link between two is important study. We aimed evaluate whether NASH an independent factor of cardiac dysfunction investigate age dependent effects on function. C57Bl/6 J middle aged (10 months old) mice (24 were fed either control or choline deficient (CDAA) diet for 8 weeks. Before termination, echocardiography was performed. Upon organ samples isolated histological molecular analysis. CDAA led development in both groups, without inducing weight gain, allowing study direct effect Mice developed hepatomegaly, fibrosis, inflammation. Aged animals had increased weight. Conventional revealed normal systolic function all cohorts, while left ventricular volumes mice. Two-dimensional speckle tracking showed subtle diastolic deterioration NASH. Histologic analyses cross-sectional area, pronounced fibrosis Col1a1 gene expression, elevated intracardiac CD68