Abstract 12452: Reduced Bdnf Attenuates Early Inflammation Aad Improves Long-term Survival Following Myocardial Infarction in Mice
Brain-derived neurotrophic factor (BDNF) increases in failing hearts, but BDNF roles in cardiac remodeling following myocardial infarction (MI) have not been investigated. BDNF heterozygous (HET, n=76) and wild type (C57BL/6) littermate (WT, n=71) male mice at the age of 6-9 months old were subjected to permanent coronary artery occlusion and evaluated at 1, 3, 5, 7 and 28 days (d) post-MI. WT and HET mice had similar infarct sizes at d 1 post-MI (46±1% vs 50±1%, p=0.14), and both groups demonstrated similar infarct wall thinning. At d 28 post-MI, fractional shortening was 2±1% in the WT mice, and this reduction was attenuated in HET mice (4±1%; p<0.05). Surprisingly, the 28 d post-MI survival rate was 40% (8/20) for WT and 76% (13/17) for HET mice (p<0.05). Plasma proteomic profiling of 58 analytes revealed that at d 1 post-MI, levels of matrix metalloproteinase (MMP)-9 (129±11 vs 96±4 ng/ml) and myeloperoxidase (MPO) (183±13 vs 147±7 ng/ml) were increased in WT compared to d 0 controls. These increases were attenuated in the HET mice. Interestingly, monocyte chemotactic protein (MCP)-1 levels were elevated in HET d 1 plasma (228±25 pg/ml) compared to WT (178±24 pg/ml) and d 0 HET (51±5 pg/ml; all p<0.05). Likewise, MCP-5 was also increased in HET d 1 compared to WT d 1 post-MI (p<0.05). Neutrophil infiltration peaked at d 1 and 3 in WT mice, but this infiltration was blunted in the HET mice. Consistent with the increased MCP-1 and MCP-5 levels in the d 1 HET plasma, macrophage infiltration at d 5 was enhanced in HET compared to WT mice. Furthermore, endothelial cell staining in d 28 post-MI sections showed lower vascularization in the infarct area in HET mice compared to WT mice. In conclusion, reduced BDNF levels modulate the early inflammatory response, leading to improved survival and reduced cardiac remodeling but reduced vascularization post-MI.
- © 2012 by American Heart Association, Inc.