Common Markers of Muscle Damage are Associated with Divergent Gene Expression Patterns after Eccentric Contractions

Abstract

Purpose Unaccustomed eccentric (ECC) exercise evokes exercise-induced muscle damage (EIMD). Soreness, strength loss and serum creatine kinase (CK) are often used to quantify EIMD severity. However, changes in these markers are not fully understood mechanistically. To test the hypothesis that muscle damage markers are associated with unique molecular processes, we correlated gene expression responses with variation in each marker post-ECC. Methods Vastus lateralis biopsies were collected from 35 young men 3-hr post-ECC (10 sets of 10 maximal eccentric contractions; contralateral leg (CON) as control). Maximal isometric strength, soreness, and serum creatine kinase activity were assessed 24 h pre-exercise and every 24 hours for 5 days post-ECC. Strength was also measured 10-minutes post-ECC. Over the five days following ECC, average peak strength loss was 51.5 ± 20%; average soreness increased from 0.9 ± 1.9 on a 100 mm visual analog scale to 39 ± 19; serum CK increased from 160 ± 130 to 1,168 ± 3,430 U/L. Muscle RNA was used to generate gene expression profiles. Partek Genomics Suite correlated peak values of soreness, strength loss and CK post-ECC with gene expression in ECC (relative to paired CON) using Pearson linear correlation (p < 0.05) and repeated measures analysis or variance used to detect influence of ECC. Results After ECC, 2677 genes correlated with peak soreness; 3333 genes with peak strength loss; and 3077 genes with peak CK. Less than 1% overlap existed across all markers (16/9087). Unique genes included 2346 genes for peak soreness, 3032 genes for peak strength loss, and 2937 genes for peak CK. Conclusions The largely unique molecular pathways associated with common indirect markers of EIMD indicates that each marker of “damage” represents unique mechanistic processes.