title: PBMCs express a transcriptome signature predictor of oxygen uptake responsiveness to endurance exercise training in men.
abstract: Peripheral blood cells are an accessible environment in which to visualize exercise-induced alterations in global gene expression patterns. We aimed to identify a peripheral blood mononuclear cell (PBMC) signature represented by alterations in gene expression, in response to a standardized endurance exercise training protocol. In addition, we searched for molecular classifiers of the variability in oxygen uptake (V̇o2). Healthy untrained policemen recruits (n = 13, 25 ± 3 yr) were selected. Peak V̇o2 (measured by cardiopulmonary exercise testing) and total RNA from PBMCs were obtained before and after 18 wk of running endurance training (3 times/wk, 60 min). Total RNA was used for whole genome expression analysis using Affymetrix GeneChip Human Gene 1.0 ST. Data were normalized by the robust multiarray average algorithm. Principal component analysis was used to perform correlations between baseline gene expression and V̇o2peak. A set of 211 transcripts was differentially expressed (ANOVA, P < 0.05 and fold change > 1.3). Functional enrichment analysis revealed that transcripts were mainly related to immune function, cell cycle processes, development, and growth. Baseline expression of 98 and 53 transcripts was associated with the absolute and relative V̇o2peak response, respectively, with a strong correlation (r > 0.75, P < 0.01), and this panel was able to classify the 13 individuals according to their potential to improve oxygen uptake. A subset of 10 transcripts represented these signatures to a similar extent. PBMCs reveal a transcriptional signature responsive to endurance training. Additionally, a baseline transcriptional signature was associated with changes in V̇o2peak. Results might illustrate the possibility of obtaining molecular classifiers of endurance capacity changes through a minimally invasive blood sampling procedure.
authors.affiliation: Laboratory of Genetics and Molecular Cardiology, Heart Institute (InCor) University of São Paulo Medical School, São Paulo, Brazil; and diasrg99@yahoo.com.br.
authors.forename: Rodrigo Gonçalves
authors.initials: RG
authors.lastname: Dias
authors.affiliation: Laboratory of Genetics and Molecular Cardiology, Heart Institute (InCor) University of São Paulo Medical School, São Paulo, Brazil; and.
authors.forename: Michelle Sabrina Moreira
authors.initials: MS
authors.lastname: Silva
authors.affiliation: Laboratory of Genetics and Molecular Cardiology, Heart Institute (InCor) University of São Paulo Medical School, São Paulo, Brazil; and.
authors.forename: Nubia Esteban
authors.initials: NE
authors.lastname: Duarte
authors.affiliation: Laboratory of Genetics and Molecular Cardiology, Heart Institute (InCor) University of São Paulo Medical School, São Paulo, Brazil; and.
authors.forename: Wladimir
authors.initials: W
authors.lastname: Bolani
authors.affiliation: School of Physical Education and Sport, University of São Paulo, São Paulo, Brazil;
authors.forename: Cleber Renê
authors.initials: CR
authors.lastname: Alves
authors.affiliation: Laboratory of Genetics and Molecular Cardiology, Heart Institute (InCor) University of São Paulo Medical School, São Paulo, Brazil; and São Paulo State Police Department, São Paulo, Brazil.
authors.forename: José Ribeiro Lemos
authors.initials: JR
authors.lastname: Junior
authors.affiliation: Laboratory of Genetics and Molecular Cardiology, Heart Institute (InCor) University of São Paulo Medical School, São Paulo, Brazil; and.
authors.forename: Jeferson Luis
authors.initials: JL
authors.lastname: da Silva
authors.affiliation: Unit of Cardiac Rehabilitation and Exercise Physiology, 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: Patrícia Alves
authors.initials: PA
authors.lastname: de Oliveira
authors.affiliation: Unit of Cardiac Rehabilitation and Exercise Physiology, Heart Institute (InCor) University of São Paulo Medical School, São Paulo, Brazil;
authors.forename: Guilherme Barreto
authors.initials: GB
authors.lastname: Alves
authors.affiliation: School of Physical Education and Sport, University of São Paulo, São Paulo, Brazil;
authors.forename: Edilamar Menezes
authors.initials: EM
authors.lastname: de Oliveira
authors.affiliation: University of Campinas, São Paulo, Brazil; and.
authors.forename: Cristiane Souza
authors.initials: CS
authors.lastname: Rocha
authors.affiliation: Laboratory of Genetics and Molecular Cardiology, Heart Institute (InCor) University of São Paulo Medical School, São Paulo, Brazil; and.
authors.forename: Julia Daher Carneiro
authors.initials: JD
authors.lastname: Marsiglia
authors.affiliation: Unit of Cardiac Rehabilitation and Exercise Physiology, 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 Eduardo
authors.initials: CE
authors.lastname: Negrao
authors.affiliation: Laboratory of Genetics and Molecular Cardiology, Heart Institute (InCor) University of São Paulo Medical School, São Paulo, Brazil; and.
authors.forename: Eduardo Moacyr
authors.initials: EM
authors.lastname: Krieger
authors.affiliation: Laboratory of Genetics and Molecular Cardiology, Heart Institute (InCor) University of São Paulo Medical School, São Paulo, Brazil; and.
authors.forename: José Eduardo
authors.initials: JE
authors.lastname: Krieger
authors.affiliation: Laboratory of Genetics and Molecular Cardiology, Heart Institute (InCor) University of São Paulo Medical School, São Paulo, Brazil; and.
authors.forename: Alexandre Costa
authors.initials: AC
authors.lastname: Pereira
mesh_terms: D000328:Adult; D000465:Algorithms; D015444:Exercise / Q000502:physiology*; D005080:Exercise Test / Q000379:methods; D005786:Gene Expression Regulation; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000502:physiology*; D008297:Male; D010101:Oxygen Consumption / Q000502:physiology; D010807:Physical Endurance / Q000235:genetics* / Q000502:physiology; D012420:Running; D059467:Transcriptome
keywords: cardiopulmonary exercise test; global gene expression; peripheral blood mononuclear cell; transcriptional signature