Common Muscle Damage Markers Are Associated With Divergent Gene Expression Changes After Eccentric Exercise

PURPOSE: Unaccustomed eccentric (ECC) exercise results in exercise-induced muscle damage (EIMD). Soreness, strength loss and serum creatine kinase (CK) levels are often used to evaluate the extent of EIMD, however, changes in these markers are not fully understood at the mechanistic level. In this study, we leveraged variation in each indirect marker following standardized exercise using correlated gene expression to gain insight into the different processes involved in each and their relationship to each other, with the hypothesis that unique molecular pathways drive each response. METHODS: Vastus lateralis biopsies were collected (N = 35) from young men 3 hr post-ECC exercise (non-exercised contralateral leg (CON) as a control). Maximal isometric strength measured on a Biodex isokinetic dynamometer, soreness measure via visual analog scale, and serum creatine kinase were assessed 24 h pre- exercise, 0 h post-exercise, and every 24 hours for 5 days following exercise. RNA from muscle biopsies was used to generate global gene expression profiles (Agilent Whole Genome Microarrays). Partek Genomics Suite correlated peak values of soreness, strength loss and CK post-ECC (0-5d) with gene expression in ECC relative to intra-subject paired CON using Pearson linear correlation. One-way RM ANOVA was used to examine the effect of time on each marker. RESULTS: We detected the following correlations (all p < 0.05) after ECC: 2677 genes with peak soreness, 3333 genes with peak strength loss, and 3077 genes with peak CK. Of the 9087 genes correlated with ECC, only 16 (0.17%) are shared between all three markers. Unique genes for each marker were: 2346 genes (88%) for peak soreness, 3032 genes (91%) for peak strength loss, 2937 genes (95%) for peak CK. CONCLUSION: In a model of moderate exercise-induced muscle damage, we related early changes in gene expression to variation in common indirect markers of muscle damage. Our results suggest that changes in these markers are the result of distinct biological processes with little shared variance between markers. Top pathways correlated with key markers include GABA receptor signaling, serotonin receptor signaling, and cAMP mediated signaling with peak strength loss. As well as NF-κβ signaling and actin cytoskeleton remodeling with peak soreness.