J Cell Mol Med. 2025 Dec;29(23):e70984. doi: 10.1111/jcmm.70984.
ABSTRACT
Myocardial infarction (MI) is a sudden necrosis of cardiomyocytes, often caused by atherosclerosis, with obesity being a significant risk factor. This study aimed to evaluate the effects of a high-fat diet (HFD) on post-MI myocardial remodelling, focusing on inflammatory signalling, nitric oxide synthase (NOS) dysregulation and oxidative stress. Nine-week-old Wistar Kyoto rats fed a control diet or a HFD for 4 weeks, followed by 20 min of left descending coronary artery occlusion and 7 days of reperfusion. Plasma levels of the proinflammatory cytokines TNF-α and IL-6 were measured using a Bioplex kit. NOS activity was assessed via [3H]-l-citrulline production, while the expression of eNOS, iNOS, NFκB and TLR4 in cardiac tissue was analysed by Western blot. Lipid peroxidation was assessed by measuring conjugated diene concentrations in cardiac tissue. MI and HFD both increased proinflammatory cytokine levels, reduced NOS activity and eNOS expression and increased iNOS expression. NFκB was more highly expressed after MI in control-fed animals. Notably, TLR4 expression was reduced by HFD and remained unchanged post-MI. Conjugated dienes were elevated post-MI and further increased by HFD. These findings demonstrate that HFD exacerbates post-MI inflammation and oxidative stress, impairing nitric oxide signalling and promoting adverse cardiac remodelling.
PMID:41387361 | DOI:10.1111/jcmm.70984