CHANGES IN SERUM MATRIX METALLOPROTEINASES AND THEIR INHIBITORS FOLLOWING ECCENTRIC MUSCLE CONTRACTIONS IN HUMANS

Abstract

Matrix metalloproteinase (MMP)-2 and −9 degrade collagen IV, the principal component of skeletal muscle basement membrane, while tissue inhibitors of metalloproteinases (TIMP) inhibit these enzymes. Studies in animals have shown remodelling of connective tissue and changes in MMP and TIMP activity in response to exercise. PURPOSE To investigate the effects of a single bout of high force eccentric contractions on concentrations of MMPs and their inhibitors in serum. METHODS Nine volunteers (5 male, 4 female, mean age 23±SD 4 yrs) each performed a single bout of 100 maximal eccentric contractions of the knee extensors of one randomly selected leg on an isokinetic dynamometer. Venepuncture blood samples were collected from the volunteers pre-exercise and on days 1, 2, 3, 4, 8, 11 and 14 post exercise. Maximum voluntary contractile (MVC) force was also recorded on these days. Serum creatine kinase (CK) activity was measured and concentrations of MMP-9, TIMP-1, TIMP-2 and the MMP-2/TIMP-2 complex were determined by enzyme linked immunosorbent assay (ELISA). Data were analysed for statistical significance using repeated measures ANOVA. RESULTS The largest decline in MVC force (39.2±23.4\%, mean±SD) was observed on day 2 post exercise. Serum CK activity (mean±SD) increased from 216±149 U • L−1 to 11, 121±17,124 U • L−1 on day 4 post exercise (P<0.01). Serum MMP-9 increased from 111±42ng• ml−1 to 188± 49ng• ml−1 on day 8 post exercise (P<0.01). When compared with the pre-exercise value, serum TIMP-1 was significantly elevated on days 1, 2, 3, 4 and 14 post exercise (P<0.05). There were no changes in serum TIMP-2 or the MMP-2/TIMP-2 complex. CONCLUSION Eccentric contraction-induced muscle damage is associated with delayed and prolonged increases in serum concentrations of MMP-9 and TIMP-1, suggestive of muscle connective tissue remodelling.