Matrix Metalloproteinases and Their Inhibitors in Chronic Obstructive Pulmonary Disease
- 753 Downloads
Chronic obstructive pulmonary disease (COPD) is characterised by irreversible airflow limitation associated with chronic inflammation. Matrix metalloproteinases (MMPs) are proteolytic enzymes that contribute to the inflammatory response in COPD and degrade extracellular matrix components. Their enzymatic activity is inhibited by a four-member family of tissue inhibitors of metalloproteinases (TIMPs). In COPD, the MMP/TIMP network, mainly MMP-9, has been repeatedly observed to be dysregulated at both the local (lung) and systemic levels. Here, we review the findings reported in numerous cross-sectional studies with our primary focus on longitudinal observations in human COPD studies. The data from longitudinal prospective studies on the MMP/TIMP network may lead to the introduction of novel prognostic biomarkers into clinical management of COPD. We address the relationship between the systemic and local lung MMP/TIMP network in COPD patients and briefly describe the involvement of microRNAs. Finally, the role of the MMP/TIMP network in COPD treatment is discussed.
KeywordsChronic obstructive pulmonary disease Matrix metalloproteinases Tissue inhibitors of metalloproteinases MicroRNAs Local and systemic response Biomarker
This work was supported by the project CZ.1.07/2.3.00/30.0004 and IGA PU LF 2015 020.
- Beasley V, Joshi PV, Singanayagam A et al (2012) Lung microbiology and exacerbations in COPD. Int J Chron Obstr Pulmon Dis 7:555–569Google Scholar
- Chaudhuri R, McSharry C, Brady J et al (2012) Sputum matrix metalloproteinase-12 in patients with chronic obstructive pulmonary disease and asthma: relationship to disease severity. J Allergy Clin Immunol 129(655–663):e658Google Scholar
- Devenport NA, Reynolds JC, Parkash V et al (2011) Determination of free desmosine and isodesmosine as urinary biomarkers of lung disorder using ultra performance liquid chromatography-ion mobility-mass spectrometry. J Chromatogr B Analyt Technol Biomed Life Sci 879:3797–3801PubMedCrossRefGoogle Scholar
- Global Strategy for the Diagnosis, Management and Prevention of COPD, Global Initiative for Chronic Obstructive Lung Disease (GOLD) (2015) http://www.goldcopd.org/
- Ilumets H, Rytilä P, Demedts I et al (2007) Matrix metalloproteinases -8, -9 and -12 in smokers and patients with stage 0 COPD. Int J Chron Obstruct Pulm Dis 2:369–379Google Scholar