RESUMO
BACKGROUND: Resistance training confers numerous health benefits that are mediated in part by circulating factors. Towards an enhanced molecular understanding, there is growing interest in a class of signaling biomarkers called extracellular vesicles (EVs). Extracellular vesicles support physiological adaptations to exercise by transporting their cargo (e.g., microRNA [miRNA]) to target cells. Previous studies of changes in EV cargo have focused on aerobic exercise, with limited data examining the effects of resistance exercise. We examined the effect of acute resistance exercise on circulating EV miRNAs and their predicted target pathways. METHODS: Ten participants (5 men; age: 26.9 ± 5.5 y, height: 1.7 ± 0.1 m, body mass: 74.0 ± 11.1 kg, body fat: 25.7 ± 11.6 %) completed an acute heavy resistance exercise test (AHRET) consisting of six sets of 10 repetitions of back squats using 75% one-repetition maximum. Pre-/post-AHRET, EVs were isolated from plasma using size exclusion chromatography, and RNA sequencing was performed. Differentially expressed (DE) miRNAs between pre- and post-AHRET EVs were analyzed using Ingenuity Pathway Analysis to predict target messenger RNAs and their target biological pathways. RESULTS: Overall, 34 miRNAs were altered by AHRET (p < 0.05), targeting 4,895 mRNAs, with enrichment of 175 canonical pathways (p < 0.01), including 12 related to growth/metabolism (p53, IGF-I, STAT3, PPAR, JAK/STAT, growth hormone, WNT/ß-catenin, ERK/MAPK, AMPK, mTOR, and PI3K/AKT) and eight to inflammation signaling (TGF-ß, IL-8, IL-7, IL-3, IL-6, IL-2, IL-17, IL-10). CONCLUSIONS: Acute resistance exercise alters EV miRNAs targeting pathways involved in growth, metabolism, and immune function. Circulating EVs may serve as significant adaptive signaling molecules influenced by exercise training.
RESUMO
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 h post-ECC (10 sets of 10 maximal eccentric contractions; contralateral leg [CON] as control). Maximal isometric strength, soreness, and serum CK activity were assessed 24 h preexercise and every 24 h for 5 d post-ECC. Strength was also measured 10 min post-ECC. Over the 5 d after 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 1168 ± 3430 U·L -1 . 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 ANOVA 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 indicate that each marker of "damage" represents unique mechanistic processes.
