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

Am J Physiol Heart Circ Physiol. 2013 Dec;305(12):H1830-42. doi: 10.1152/ajpheart.00224.2013. Epub 2013 Oct 18.


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.

Keywords: brain-derived neurotrophic factor; inflammation; myeloperoxidase; myocardial infarction; obesity; proteomic profiling.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Brain-Derived Neurotrophic Factor / genetics
  • Brain-Derived Neurotrophic Factor / metabolism*
  • Heart / drug effects
  • Heart / physiopathology*
  • Heterozygote
  • Inflammation / genetics
  • Inflammation / metabolism*
  • Male
  • Matrix Metalloproteinase 9 / metabolism
  • Mice
  • Mice, Knockout
  • Myocardial Infarction / genetics
  • Myocardial Infarction / metabolism*
  • Myocardial Infarction / physiopathology
  • Myocardium / metabolism*
  • Neovascularization, Pathologic / genetics
  • Neovascularization, Pathologic / metabolism*
  • Neutrophils / drug effects
  • Neutrophils / metabolism
  • Peroxidase / metabolism
  • Peroxidase / pharmacology
  • Vascular Endothelial Growth Factor A / metabolism


  • Brain-Derived Neurotrophic Factor
  • Vascular Endothelial Growth Factor A
  • Peroxidase
  • Matrix Metalloproteinase 9