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Increased matrix metalloproteinase-9 with elastolysis in nocturnal asthma
David N Pham1, Hong Wei Chu, Richard J Martin
1Department of Medicine, National Jewish Medical and Research Center, Denver, Colorado 80206, USA.
Summary
Nocturnal asthma patients show increased matrix metalloproteinase-9 (MMP-9) and decreased tissue inhibitor of metalloproteinase-1 (TIMP-1) at night, potentially causing reduced airway elastin. This circadian change was not observed in non-nocturnal asthma patients.
Area of Science:
- Pulmonary Medicine
- Biochemistry
- Respiratory Physiology
Background:
- Matrix metalloproteinase-9 (MMP-9) degrades elastin, while tissue inhibitor of metalloproteinase-1 (TIMP-1) inhibits it.
- Reduced airway elastin volume density was observed in nocturnal asthma (NA) compared to non-nocturnal asthma (NNA) and normal controls (NL).
Purpose of the Study:
- To investigate the hypothesis that increased metalloproteinases and decreased tissue inhibitors contribute to reduced elastin in NA airways.
- To explore the role of MMP-9 and TIMP-1 in the pathophysiology of nocturnal asthma.
Main Methods:
- Bronchoscopy with bronchoalveolar lavage was performed on NA, NNA, and NL subjects at 4:00 PM and 4:00 AM.
- Enzyme-linked immunosorbent assay (ELISA) was used to quantify levels of MMP-2, MMP-9, TIMP-1, and TIMP-2.
Main Results:
- NA subjects exhibited a fourfold circadian increase in bronchoalveolar lavage MMP-9 levels from 4:00 PM to 4:00 AM.
- The MMP-9 to TIMP-1 ratio doubled in NA subjects overnight, with significantly higher levels at 4:00 AM compared to NNA and NL groups.
- MMP-9 levels correlated with overnight decline in forced expiratory volume in 1 second (FEV1).
Conclusions:
- Increased nocturnal MMP-9 and decreased TIMP-1 in NA may be responsible for reduced airway elastin density.
- These findings suggest a potential mechanism for airway remodeling in nocturnal asthma.