Date of Award

Winter 12-30-2014

Document Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Department

Integrative Physiology

First Advisor

David L. Allen

Second Advisor

William C. Byrnes

Third Advisor

Roger Enoka

Fourth Advisor

Leslie A. Leinwand

Fifth Advisor

Robert S. Mazzeo

Abstract

Exercise induced muscle injury is a phenomenon that most adults have experienced when beginning a new or novel exercise program. It is perceived as muscle soreness developing 24-48 hours after completion of the exercise task. The role of the muscle extracellular matrix (ECM) in remodeling of muscle during the repair process following injury has recently become a focus of this area of research. Key to the remodeling of the ECM is the inducible protease, matrix metalloproteinase-9 (MMP-9) that preferentially degrades type IV collagen of the ECM. Animal models have provided support for MMP-9 in this remodeling process but the role of MMP-9 following exercise induced muscle injury in the human model remains controversial.

The purpose of this dissertation was to provide a more definitive examination of the plasma and skeletal muscle MMP-9 responses following exercise induced muscle injury in humans. To accomplish this goal, three models were used: elbow flexion, downhill running, and leg extension. Rigorous controls related to subject inclusion/exclusion criteria, exercise protocols, and methods for measurements, were incorporated into each of the studies to address confounds in previous work. Unlike previous studies, a test-retest measure was added to provide information on the stability of the dependent measures from day-to-day.

We consistently found a significant increase in plasma MMP-9 immediately after eccentric exercise, but the magnitude was small and rarely exceeded the variation measured from day-to-day. We concluded that plasma MMP-9 is not an adequate marker of muscle damage, but this does not preclude a role at the level of the tissue. Inside muscle, we found signs of ECM modification following eccentric actions, supporting the idea that eccentric actions stimulate ECM remodeling. The early timing of the plasma MMP-9 response, along with the presence ECM changes within muscle, is consistent with one of the proposed mechanistic roles for MMP- 9, degradation of ECM to assist with the migration and invasion of immune cells. Future work that focuses on changes inside of muscle with increased sampling time points and includes measurement of immune cells is needed to clarify the specific role of MMP-9 in exercise induced muscle injury in humans.

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