Serum levels of matrix metalloproteinase-9, tissue inhibitors of metalloproteinase-1 and their ratio are associated with impaired lung function in the elderly: a population-based study

Abstract

BACKGROUND AND OBJECTIVE: Matrix metalloproteinases (MMP) and their inhibitors, tissue inhibitors of metalloproteinases (TIMP), regulate homeostasis and turnover of the extra cellular matrix. The aim of this study was to investigate the associations of serum MMP-9 and TIMP-1 with lung function. METHODS: Spirometry was performed in a population-based sample of 888 subjects aged 70 years. Serum MMP-9 and TIMP-1 concentrations were measured by ELISA. RESULTS: Lower FEV(1) values were associated with higher serum levels of MMP-9 (P = 0.001) and TIMP-1 (P < 0.001), and a higher ratio of MMP-9 to TIMP-1 (P = 0.02). These associations were significant after adjustment for gender, weight, height, BMI, current smoking, pack years of smoking and the time for which samples were frozen. After stratification for gender, the associations between FEV(1) and MMP-9, TIMP-1, and their ratio, were significant in men but not in women. CONCLUSIONS: Lower FEV(1) was significantly but weakly associated with higher serum levels of MMP-9, TIMP-1 and a higher MMP-9/TIMP-1 ratio. This association was stronger in men than in women, suggesting a possible role for extracellular matrix remodelling in the development of impaired lung function. These associations may also partly explain the association between low FEV(1) and cardiovascular disease.