title: Peripheral vascular reactivity and serum BDNF responses to aerobic training are impaired by the BDNF Val66Met polymorphism.
abstract: Besides neuronal plasticity, the neurotrophin brain-derived neurotrophic factor (BDNF) is also important in vascular function. The BDNF has been associated with angiogenesis through its specific receptor tropomyosin-related kinase B (TrkB). Additionally, Val66Met polymorphism decreases activity-induced BDNF. Since BDNF and TrkB are expressed in vascular endothelial cells and aerobic exercise training can increase serum BDNF, this study aimed to test the hypotheses: 1) Serum BDNF levels modulate peripheral blood flow; 2) The Val66Met BDNF polymorphism impairs exercise training-induced vasodilation. We genotyped 304 healthy male volunteers (Val66Val, n = 221; Val66Met, n = 83) who underwent intense aerobic exercise training on a running track three times/wk for 4 mo. We evaluated pre- and post-exercise training serum BDNF and proBDNF concentration, heart rate (HR), mean blood pressure (MBP), forearm blood flow (FBF), and forearm vascular resistance (FVR). In the pre-exercise training, BDNF, proBDNF, BDNF/proBDNF ratio, FBF, and FVR were similar between genotypes. After exercise training, functional capacity (V̇o2 peak) increased and HR decreased similarly in both groups. Val66Val, but not Val66Met, increased BDNF (interaction, P = 0.04) and BDNF/proBDNF ratio (interaction, P < 0.001). Interestingly, FBF (interaction, P = 0.04) and the FVR (interaction, P = 0.01) responses during handgrip exercise (HG) improved in Val66Val compared with Val66Met, even with similar responses of HR and MBP. There were association between BDNF/proBDNF ratio and FBF (r = 0.64, P < 0.001) and FVR (r = -0.58, P < 0.001) during HG exercise. These results show that peripheral vascular reactivity and serum BDNF responses to exercise training are impaired by the BDNF Val66Met polymorphism and such responsiveness is associated with serum BDNF concentrations in healthy subjects.
authors.affiliation: School of Physical Education, Military Police of São Paulo State, São Paulo, Brazil; Heart Institute (InCor), University of São Paulo Medical School, São Paulo, Brazil;
authors.forename: José R
authors.initials: JR
authors.lastname: Lemos
authors.affiliation: School of Physical Education and Sport, University of São Paulo, São Paulo, Brazil;
authors.forename: Cleber R
authors.initials: CR
authors.lastname: Alves
authors.affiliation: Heart Institute (InCor), University of São Paulo Medical School, São Paulo, Brazil;
authors.forename: Sílvia B C
authors.initials: SB
authors.lastname: de Souza
authors.affiliation: Heart Institute (InCor), University of São Paulo Medical School, São Paulo, Brazil;
authors.forename: Julia D C
authors.initials: JD
authors.lastname: Marsiglia
authors.affiliation: Heart Institute (InCor), University of São Paulo Medical School, São Paulo, Brazil;
authors.forename: Michelle S M
authors.initials: MS
authors.lastname: Silva
authors.affiliation: Heart Institute (InCor), University of São Paulo Medical School, São Paulo, Brazil;
authors.forename: Alexandre C
authors.initials: AC
authors.lastname: Pereira
authors.affiliation: Federal University of Minas Gerais, Minas Gerais, Brazil; and.
authors.forename: Antônio L
authors.initials: AL
authors.lastname: Teixeira
authors.affiliation: Federal University of Minas Gerais, Minas Gerais, Brazil; and.
authors.forename: Erica L M
authors.initials: EL
authors.lastname: Vieira
authors.affiliation: Heart Institute (InCor), University of São Paulo Medical School, São Paulo, Brazil;
authors.forename: José E
authors.initials: JE
authors.lastname: Krieger
authors.affiliation: Heart Institute (InCor), University of São Paulo Medical School, São Paulo, Brazil; School of Physical Education and Sport, University of São Paulo, São Paulo, Brazil;
authors.forename: Carlos E
authors.initials: CE
authors.lastname: Negrão
authors.affiliation: Heart Institute (InCor), University of São Paulo Medical School, São Paulo, Brazil;
authors.forename: Guilherme B
authors.initials: GB
authors.lastname: Alves
authors.affiliation: School of Physical Education and Sport, University of São Paulo, São Paulo, Brazil;
authors.forename: Edilamar M
authors.initials: EM
authors.lastname: de Oliveira
authors.affiliation: Heart Institute (InCor), University of São Paulo Medical School, São Paulo, Brazil;
authors.forename: Wladimir
authors.initials: W
authors.lastname: Bolani
authors.affiliation: Heart Institute (InCor), University of São Paulo Medical School, São Paulo, Brazil;
authors.forename: Rodrigo G
authors.initials: RG
authors.lastname: Dias
authors.affiliation: Heart Institute (InCor), University of São Paulo Medical School, São Paulo, Brazil; Universidade Nove de Julho (UNINOVE), São Paulo, Brazil ivani.trombetta@gmail.com.
authors.forename: Ivani C
authors.initials: IC
authors.lastname: Trombetta
mesh_terms: D000328:Adult; D001783:Blood Flow Velocity; D001794:Blood Pressure; D019208:Brain-Derived Neurotrophic Factor / Q000097:blood* / Q000235:genetics*; D015444:Exercise; D005080:Exercise Test; D005542:Forearm / Q000098:blood supply; D005838:Genotype; D018737:Hand Strength; D064368:Healthy Volunteers; D006339:Heart Rate; D006801:Humans; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics; D008715:Methionine / Q000235:genetics; D011110:Polymorphism, Genetic; D011505:Protein-Tyrosine Kinases / Q000235:genetics; D020813:Receptor, trkB; D014633:Valine / Q000235:genetics; D055815:Young Adult
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D008562:Membrane Glycoproteins; C579455:BDNF protein, human; D008715:Methionine; D011505:Protein-Tyrosine Kinases; D020813:Receptor, trkB; C000591259:tropomyosin-related kinase-B, human; D014633:Valine
keywords: BDNF Val66Met polymorphism; exercise training; vascular reactivity