title: Reduced BDNF attenuates inflammation and angiogenesis to improve survival and cardiac function following myocardial infarction in mice.
abstract: 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.
authors.affiliation: San Antonio Cardiovascular Proteomics Center, San Antonio, Texas;
authors.forename: Ganesh V
authors.initials: GV
authors.lastname: Halade
authors.forename: Yonggang
authors.initials: Y
authors.lastname: Ma
authors.forename: Trevi A
authors.initials: TA
authors.lastname: Ramirez
authors.forename: Jianhua
authors.initials: J
authors.lastname: Zhang
authors.forename: Qiuxia
authors.initials: Q
authors.lastname: Dai
authors.forename: Julie G
authors.initials: JG
authors.lastname: Hensler
authors.forename: Elizabeth F
authors.initials: EF
authors.lastname: Lopez
authors.forename: Omid
authors.initials: O
authors.lastname: Ghasemi
authors.forename: Yu-Fang
authors.initials: YF
authors.lastname: Jin
authors.forename: Merry L
authors.initials: ML
authors.lastname: Lindsey
mesh_terms: D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics / Q000378:metabolism*; D006321:Heart / Q000187:drug effects / Q000503:physiopathology*; D006579:Heterozygote; D007249:Inflammation / Q000235:genetics / Q000378:metabolism*; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D009203:Myocardial Infarction / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D009206:Myocardium / Q000378:metabolism*; D009389:Neovascularization, Pathologic / Q000235:genetics / Q000378:metabolism*; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism; D009195:Peroxidase / Q000378:metabolism / Q000494:pharmacology; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D042461:Vascular Endothelial Growth Factor A; D009195:Peroxidase; D020780:Matrix Metalloproteinase 9
keywords: brain-derived neurotrophic factor; inflammation; myeloperoxidase; myocardial infarction; obesity; proteomic profiling