Gelatinases and physical exercise A systematic review of evidence from human studies

Background: Matrix metalloproteinases (MMPs), particularly gelatinase A (MMP-2) and gelatinase B (MMP-9), as well as their tissue inhibitors (TIMP-1 and TIMP-2), are involved in the development of skeletal muscle tissue, in the repair process after muscle injury and in the adaptive modifications induced by physical exercise in skeletal muscle. This paper aims at reviewing results from human studies that investigated the role of gelatinases and their inhibitors in skeletal muscle response to acute physical exercise or training. Methods: Electronic databases PubMed/MEDLINE, Scopus and Web of Science were searched for papers published between January 2000 and February 2017. The papers were eligible when reporting human studies in which MMP-2 and/or MMP-9 and/or the inhibitors TIMP-1/TIMP-2 were evaluated, in blood or muscular tissue, before and after acute physical exercise or before and after a period of structured physical training. We included studies on healthy subjects and patients with chronic metabolic diseases (obesity, diabetes mellitus, metabolic syndrome-MS) or asymptomatic coronary artery disease. We excluded studies on patients with neurological, rheumatologic or neoplastic diseases. Results: Studies conducted on muscle biopsies showed an early stimulation of MMP-9 gene transcription as a result of acute exercise, whereas MMP-2 and TIMP transcription resulted from regular repetition of exercise over time. Studies on serum or plasma level of gelatinases and their inhibitors showed an early release of MMP-9 after acute exercise of sufficient intensity, while data on MMP-2 and TIMP were more contrasting. Most of the studies dealing with the effect of training indicated a trend toward reduction in blood gelatinase levels, once again more clear for MMP-9. This result was related to an anti-inflammatory effect of regular exercise and was more evident when training consisted of aerobic activities. This study has limitations: as the initial selection was done through titles and abstracts, incomplete retrieval cannot be excluded, as well as we cannot exclude bias due to selective reporting within studies. Conclusion: A better knowledge of the molecular events activated by different types of acute exercise and regular training could be of great relevance in order to maximize the benefits of physical activity in healthy subjects and patients.