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1 Research Center for Genetic Medicine, Children's National Medical Center and George Washington University, Washington, DC, USA
2 Department of Exercise Science, University of Massachusetts, Amherst, MA, USA
3 Department of Preventive Cardiology, Hartford Hospital, Hartford, CT, USA
* To whom correspondence should be addressed. E-mail: clarkson{at}excsci.umass.edu.
We examined the effect of eccentric exercise on the transcriptome of skeletal muscle in three male human volunteers who performed 300 concentric contractions with one leg and 300 eccentric contractions with the opposite leg. Vastus lateralis muscle biopsies were taken from both legs at 4-8 hours after exercise and expression profiled using 12,000 gene Affymetrix U95A microarrays. We found a high concordance of expression responses to eccentric contractions between our human and rat data from a previous study (11) (approximately 50% of gene expression changes shared between species). Potential human-specific changes included greater inflammatory responses (chemokine [C-C motif] ligand 2 [CCL2], C/EBP delta [CEBPD] and interleukin 1 receptor [IL1R1]) and vascular remodeling (tenascin C and lipocortin II). Induction of c-fos and lipocortin II were confirmed at the protein level, with c-fos localized to myofiber nuclei and lipocortin II to intramuscular capillaries. We also confirmed the eccentric-induced expression of six transcripts by quantitative RT-PCR (CARP, CCL2, CEBPD, IL1R1, tenascin C, and cysteine-rich angiogenic inducer 61 [CYR61]). These data provide the first characterization of the transcriptional response of skeletal muscle to eccentric exercise in humans, and represent a preliminary step in understanding the molecular processes underlying muscle remodeling (including a new focus on rapid changes in the capillary bed) and inflammatory responses following damaging lengthening contractions.
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