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Cited by 135Cardiovascular and exercise physiologyGenetics and Physical PerformanceExercise and Physiological Responses

Modulation of extracellular matrix genes reflects the magnitude of physiological adaptation to aerobic exercise training in humans

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Timmons, James A, Jansson, Eva, Fischer, Helene, Gustafsson, Thomas, Greenhaff, Paul L, Ridden, John, Rachman, Jonathan, Sundberg, Carl Johan·2005·BMC Biology
DOI 10.1186/1741-7007-3-19PMC PMC1224855
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Abstract

Background: Regular exercise reduces cardiovascular and metabolic disease partly through improved aerobic fitness. The determinants of exercise-induced gains in aerobic fitness in humans are not known. We have demonstrated that over 500 genes are activated in response to endurance-exercise training, including modulation of muscle extracellular matrix (ECM) genes. Real-time quantitative PCR, which is essential for the characterization of lower abundance genes, was used to examine 15 ECM genes potentially relevant for endurance-exercise adaptation. Twenty-four sedentary male subjects undertook six weeks of high-intensity aerobic cycle training with muscle biopsies being obtained both before and 24 h after training. Subjects were ranked based on improvement in aerobic fitness, and two cohorts were formed (n = 8 per group): the high-responder group (HRG; peak rate of oxygen consumption increased by +0.71 ± 0.1 L min -1 ; p < 0.0001) while the low-responder group (LRG; peak rate of oxygen consumption did not change, +0.17 ± 0.1 L min -1 , ns). ECM genes profiled included the angiopoietin 1 and related genes ( angiopoietin 2 , tyrosine kinase with immunoglobulin-like and EGF-like domains 1 (TIE1) and 2 ( TIE2 ), vascular endothelial growth factor ( VEGF ) and related receptors ( VEGF receptor 1, VEGF receptor 2 and neuropilin-1 ), thrombospondin-4 , α2-macroglobulin and transforming growth factor β2 . Results: neuropilin-1 (800%; p < 0.001) and VEGF receptor 2 (300%; p < 0.01) transcript abundance increased only in the HRG, whereas levels of VEGF receptor 1 mRNA actually declined in the LRG (p < 0.05). TIE1 and TIE2 mRNA levels were unaltered in the LRG, whereas transcription levels of both genes were increased by 2.5-fold in the HRG (p < 0.01). Levels of thrombospondin-4 (900%; p < 0.001) and α2-macroglobulin (300%, p < 0.05) mRNA increased substantially in the HRG. In contrast, the amount of transforming growth factor β2 transcript increased only in the HRG (330%; p < 0.01), whereas it remained unchanged in the LRG (-80%). Conclusion: We demonstrate for the first time that aerobic training activates angiopoietin 1 and TIE2 genes in human muscle, but only when aerobic capacity adapts to exercise-training. The fourfold-greater increase in aerobic fitness and markedly differing gene expression profile in the HRG indicates that these ECM genes may be critical for physiological adaptation to exercise in humans. In addition, we show that, without careful demonstration of physiological adaptation, conclusions derived from gene expression profiling of human skeletal muscle following exercise may be of limited value. We propose that future studies should (a) investigate the mechanisms that underlie the apparent link between physiological adaptation and gene expression and (b) use the genes profiled in this paper as candidates for population genetic studies.

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  • Low responders to each exercise stimulus may be as high as 25% in studies of individuals undertaking resistance and endurance training in isolation.

    “The characterisation of individual responses is not a new phenomenon, but the results of studies of individuals undertaking resistance and endurance training in isolation suggest that 'low responders' to each exercise stimulus may be as high as 25% (Timmons et al., 2005;Phillips et al., 2013;Gurd et al., 2016).”

    From Concurrent exercise training: do opposites distract? (2017) · cites this paper as Timmons et al., 2005

    The Methods (Human and physiological measurements; page not supplied) describe a low-responder group selected after supervised endurance training, supporting the existence of low responders to that stimulus. The group was selected from a larger cohort, so its size does not establish that 25% of trainees were low responders. This paper did not study responses to resistance training. (LLM, conf=0.87)

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Authors
Timmons, J. A., Jansson, E., Fischer, H., Gustafsson, T., Greenhaff, P. L., Ridden, J., Rachman, J., & Sundberg, C. J.
Affiliations
  • Karolinska Institutet (SE)
  • University of Nottingham (GB)
  • AstraZeneca (United Kingdom) (GB)
Corresponding author
Timmons, James A
ORCID
Venue
BMC Biology
Publisher
Springer Science and Business Media LLC
Published
2005-09-02
Volume
3
Issue
1
Pages
19-19
ISSN
1741-7007 (ISSN-L)
DOI
10.1186/1741-7007-3-19
PMC
PMC1224855
OpenAlex
W1527271891
Cited by
135
References
55
Citations by year
2026: 3 · 2025: 1 · 2024: 4 · 2023: 5 · 2022: 6 · 2021: 6 · 2020: 5 · 2019: 6 · 2018: 9 · 2017: 3 · 2016: 9 · 2015: 5 · 2014: 8 · 2013: 10 · 2012: 7
FWCI
17.01
Type
journal article
Language
en
Open access
Licence
cc-by
Locations
  • BMC Biology (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
Funders
Medical Research Council
Topics
  • Health Sciences › Medicine › Complementary and alternative medicine › Cardiovascular and exercise physiology
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Physical Performance
  • Health Sciences › Medicine › Rehabilitation › Exercise and Physiological Responses
Keywords
aerobic exercise training, endurance training, exercise-induced gene expression, extracellular matrix genes, cardiorespiratory fitness, high responders, low responders, VEGF receptor 2, neuropilin-1, Tie1, Tie2, angiopoietin-1, angiopoietin-2, thrombospondin-4, alpha2-macroglobulin, transforming growth factor-beta2
MeSH terms
Acclimatization, Aerobiosis, Extracellular Matrix, Gene Expression Regulation, Humans, Oxygen Consumption, Physical Fitness, Exercise, Extracellular Matrix Proteins, Gene Expression Profiling, Receptors, Vascular Endothelial Growth Factor, Vascular Endothelial Growth Factor A

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