Moderate-Dose Exercise Protects Against Heart Failure via Apelin/NLRP3 Mediated Inflammation

Background: Heart failure (HF) remains a major cause of cardiovascular mortality worldwide, imposing a substantial burden on healthcare systems. Although physical exercise is known to exert cardioprotective effects, its underlying mechanisms are not fully understood. Methods: We established a post-myocardial infarction (MI) HF mouse model via coronary artery ligation, followed by an 8-week exercise regimen at different intensities. Multi-omics sequencing was performed to identify alterations in inflammatory and metabolic pathways. Results: Moderate-dose exercise preserved cardiac function and attenuated ventricular remodeling. Metabolomic analysis indicated modulation of lipid metabolism and inflammation via the Apelin pathway. Transcriptomics revealed that the nucleotide-binding oligomerization domain (NOD)-like receptor signaling pathway, which was elevated after MI, was suppressed by moderate-dose exercise. Additionally, Nuclear factor erythroid 2-related factor 2 (Nrf2)—a key transcription factor regulating antioxidant and anti-inflammatory responses—was upregulated in the moderate-exercise group. Conclusions: Moderate-dose exercise protects against HF in mice by regulating lipid metabolism and inflammatory pathways. These findings support the standardization of exercise therapy for secondary prevention of cardiovascular disease.