Reduced Bdnf Attenuates Inflammation and Angiogenesis to Improve Survival and Cardiac Function Following Myocardial Infarction in Mice
Brain-derived neurotrophic factor, Inflammation, Myeloperoxidase, Myocardial infarction, Obesity, Proteomic profiling
Digital Object Identifier (DOI)
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 mo of age were subjected to MI and evaluated at days 1, 3, 5, 7, or 28 post-MI. At day 28 post-MI, 76% of HET versus 40% of WT survived, whereas fractional shortening improved and neovascularization levels were reduced in the HET (all, P < 0.05). At day 1, post-MI, matrix metalloproteinase-9, and myeloperoxidase (MPO) increased in WT, but not in HET. Concomitantly, monocyte chemotactic protein-1 and -5 levels increased and vascular endothelial growth factor (VEGF)-A decreased in HET. Neutrophil infiltration peaked at days 1-3 in WT mice, and this increase was blunted in HET. To determine if MPO administration could rescue the HET phenotype, MPO was injected at 3 h post-MI. MPO restored VEGF-A levels without altering matrix metalloproteinase- 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 day 28 post-MI. Thus reduced BDNF attenuates early inflammation following MI by modulating MPO and angiogenic response through VEGF-A.
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Citation / Publisher Attribution
American Journal of Physiology - Heart and Circulatory Physiology, v. 305, issue 12, p. H1830-H1842
Scholar Commons Citation
Halade, Ganesh V.; Ma, Yonggang; Ramirez, Trevi A.; Zhang, Jianhua; Dai, Qiuxia; Hensler, Julie G.; Lopez, Elizabeth F.; Ghasemi, Omid; Jin, Yu Fang; and Lindsey, Merry L., "Reduced Bdnf Attenuates Inflammation and Angiogenesis to Improve Survival and Cardiac Function Following Myocardial Infarction in Mice" (2013). Internal Medicine Faculty Publications. 53.