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

Ganesh V. Halade, Yonggang Ma, Trevi A. Ramirez, Jianhua Zhang, Qiuxia Dai, Julie G. Hensler, Elizabeth F. Lopez, Omid Ghasemi, Yu Fang Jin, Merry L. Lindsey

Research output: Contribution to journalArticle

31 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)H1830-H1842
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume305
Issue number12
DOIs
StatePublished - Dec 15 2013

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Keywords

  • Brain-derived neurotrophic factor
  • Inflammation
  • Myeloperoxidase
  • Myocardial infarction
  • Obesity
  • Proteomic profiling

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

Cite this

Halade, G. V., Ma, Y., Ramirez, T. A., Zhang, J., Dai, Q., Hensler, J. G., Lopez, E. F., Ghasemi, O., Jin, Y. F., & Lindsey, M. L. (2013). Reduced BDNF attenuates inflammation and angiogenesis to improve survival and cardiac function following myocardial infarction in mice. American Journal of Physiology - Heart and Circulatory Physiology, 305(12), H1830-H1842. https://doi.org/10.1152/ajpheart.00224.2013