Reduced BDNF attenuates inflammation and angiogenesis to improve survival and cardiac function following myocardial infarction in mice

Brain‐derived neurotrophic factor (BDNF) increases in failing hearts, but BDNF roles in cardiac remodeling following myocardial infarction (MI) are unclear. Male BDNF+/+ (wild type, WT) and BDNF+/− heterozygous (HET) mice at 6–9 months of age were subjected to MI and evaluated at day (d) 1, 3, 5, 7, or 28 post‐ MI. At d28 post‐MI, 76% of HET vs. 40% of WT mice survived, while fractional shortening was improved and neovascularization levels were reduced in the HET (all p<0.05). At d1 post‐MI, matrix metalloproteinase (MMP)‐9 and myeloperoxidase (MPO) increased in WT, but not in HET. Concomitantly, monocyte chemotactic protein (MCP)‐1 and ‐5 levels increased and vascular endothelial growth factor (VEGF)‐A decreased in HET. Neutrophil infiltration peaked at d1–3 in WT mice, and this increase was blunted in HET. To determine if MPO administration could rescue the HET phenotype, MPO was injected at 3h post‐MI. MPO restored VEGF‐A levels without altering MMP‐9 or neutrophil content. In conclusion, reduced BDNF levels modulated the early inflammatory and neovascularization responses, leading to improved survival and reduced cardiac remodeling at d28 post‐MI. Thus, reduced BDNF attenuates early inflammation following MI by modulating MPO and angiogenic response through VEGF‐A.