Suppressing IL-1β signaling, depleting macrophages, or scavenging mitochondrial ROS significantly ameliorated high-fat diet-induced diastolic dysfunction in mice.
Does suppressing IL-1β signaling or depleting macrophages improve high-fat diet-induced diastolic dysfunction in mice?
Macrophage-mediated inflammation contributes to high-fat diet-associated diastolic dysfunction through IL-1β and mitochondrial ROS production, suggesting a potential therapeutic target for HFpEF.
Diabetes mellitus (DM) is a main risk factor for diastolic dysfunction (DD) and heart failure with preserved ejection fraction. High-fat diet (HFD) mice presented with diabetes mellitus, DD, higher cardiac interleukin (IL)-1β levels, and proinflammatory cardiac macrophage accumulation. DD was significantly ameliorated by suppressing IL-1β signaling or depleting macrophages. Mice with macrophages unable to adopt a proinflammatory phenotype were low in cardiac IL-1β levels and were resistant to HFD-induced DD. IL-1β enhanced mitochondrial reactive oxygen species (mitoROS) in cardiomyocytes, and scavenging mitoROS improved HFD-induced DD. In conclusion, macrophage-mediated inflammation contributed to HFD-associated DD through IL-1β and mitoROS production.
Liu et al. (Wed,) conducted a other in Heart failure with preserved ejection fraction and diastolic dysfunction. Suppressing IL-1β signaling, depleting macrophages, or scavenging mitoROS vs. Control mice on high-fat diet was evaluated on Diastolic dysfunction. Suppressing IL-1β signaling, depleting macrophages, or scavenging mitochondrial ROS significantly ameliorated high-fat diet-induced diastolic dysfunction in mice.