title: Possible role of brain-derived neurotrophic factor in the pathogenesis of coronary artery disease.
abstract: BACKGROUND
  The neurotrophin (NT) family, including nerve growth factor NT-3 and brain-derived neurotrophic factor (BDNF), has a critical role in the survival, growth, maintenance, and death of central and peripheral neurons. NTs and their receptors are expressed in atherosclerotic lesions; however, their significance in cardiovascular disease remains unclear.
  
  
  RESULTS
  To clarify the role of NTs in the pathogenesis of coronary artery disease, NT plasma levels in the aorta, coronary sinus, and peripheral veins of patients with unstable angina (n=38), stable effort angina (n=45), and non-coronary artery disease (n=24) were examined. In addition, regional expression of BDNF in coronary arteries was examined in autopsy cases and patients with angina pectoris by directional coronary atherectomy. The difference in BDNF levels, but not NT-3, between the coronary sinus and aorta was significantly greater in the unstable angina group compared with the stable effort angina and non-coronary artery disease groups. Immunohistochemical investigations demonstrated BDNF expression in the atheromatous intima and adventitia in atherosclerotic coronary arteries. BDNF expression was enhanced in macrophages and smooth muscle cells in atherosclerotic coronary arteries. Stimulation with recombinant BDNF significantly enhanced NAD(P)H oxidase activity and the generation of reactive oxygen species in cultured human coronary artery smooth muscle cells.
  
  
  CONCLUSIONS
  BDNF has an important role in atherogenesis and plaque instability via the activation of NAD(P)H oxidase.
authors.affiliation: Division of Cardiovascular and Respiratory Medicine, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe 650-0017, Japan.
authors.forename: Junya
authors.initials: J
authors.lastname: Ejiri
authors.forename: Nobutaka
authors.initials: N
authors.lastname: Inoue
authors.forename: Seiichi
authors.initials: S
authors.lastname: Kobayashi
authors.forename: Rio
authors.initials: R
authors.lastname: Shiraki
authors.forename: Kazunori
authors.initials: K
authors.lastname: Otsui
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Honjo
authors.forename: Motonori
authors.initials: M
authors.lastname: Takahashi
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Ohashi
authors.forename: Shinobu
authors.initials: S
authors.lastname: Ichikawa
authors.forename: Mitsuyasu
authors.initials: M
authors.lastname: Terashima
authors.forename: Takao
authors.initials: T
authors.lastname: Mori
authors.forename: Kojiro
authors.initials: K
authors.lastname: Awano
authors.forename: Toshiro
authors.initials: T
authors.lastname: Shinke
authors.forename: Junya
authors.initials: J
authors.lastname: Shite
authors.forename: Ken-ichi
authors.initials: K
authors.lastname: Hirata
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Yokozaki
authors.forename: Seinosuke
authors.initials: S
authors.lastname: Kawashima
authors.forename: Mitsuhiro
authors.initials: M
authors.lastname: Yokoyama
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000787:Angina Pectoris / Q000000981:diagnostic imaging* / Q000401:mortality; D001344:Autopsy; D015415:Biomarkers / Q000378:metabolism; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism*; D017023:Coronary Angiography; D003327:Coronary Disease / Q000000981:diagnostic imaging / Q000401:mortality / Q000503:physiopathology*; D023921:Coronary Stenosis / Q000000981:diagnostic imaging*; D038181:FMN Reductase / Q000378:metabolism; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D012307:Risk Factors; D012907:Smoking; D016019:Survival Analysis
chemical_list: D015415:Biomarkers; D019208:Brain-Derived Neurotrophic Factor; D038181:FMN Reductase