Twelve-week high-fat diet for improving adverse ventricular remodeling post-myocardial infarction by alleviating local inflammation

BACKGROUND: Many studies have examined how to achieve better outcomes in myocardial infarction (MI) patients with mild obesity or who are overweight. However, the influence of a high-fat diet (HFD) and the underlying mechanisms by which it can affect ventricular remodeling following MI are poorly understood. This study investigated the impact of a 12-week HFD on the left ventricular (LV) remodeling of permanent MI models and immune cell involvement. METHODS: Male C57BL/6J mice were fed HFD or normal diet (ND). After 8 weeks of feeding, mice underwent cardiac left anterior descending coronary artery ligation, and the same diet was continued for a further 4 weeks. Cardiac structure and function were detected using echocardiography. Cardiac fibrosis was evaluated using histological staining at 7 and 28 days post-MI. Infiltration of various immune cells was examined using flow cytometry and immunofluorescence at 7 days post-MI. RESULTS: Compared with a ND, the 12-week HFD feeding significantly alleviated ventricular remodeling following MI. HFD mice showed reduced infiltration of neutrophils, a higher proportion of M2/M1 macrophages, decreased conventional and monocyte-derived dendritic cells (moDCs) in the injured myocardium, and elevated levels of regulatory T cells (Tregs). Further investigation of dendritic cells (DCs) phenotypes indicated downregulated expression of major histocompatibility complex class II (MHCII). It also showed costimulatory molecules CD40 and CD86 on conventional and moDCs in mediastinal lymph nodes (mLNs). CONCLUSIONS: This study demonstrated the protective effect of a 12-week HFD on ventricular remodeling following MI via the alleviation of local inflammation.