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Published on: July 3, 2014
Metalloproteinases and Their Tissue Inhibitors in Comparison between Different Chronic Pneumopathies in the Horse
Ann Kristin Barton1, Tarek Shety1, Angelika Bondzio2
1Equine Clinic, Veterinary Faculty, Freie Universitaet Berlin, Oertzenweg 19b, 14163 Berlin, Germany.
Abstract:
In chronic respiratory disease, matrix metalloproteinases (MMPs) contribute to pathological tissue destruction when expressed in excess, while tissue inhibitors of metalloproteinases (TIMPs) counteract MMPs with overexpression leading to fibrosis formation. They may be out of balance in equine pneumopathies and serve as biomarkers of pulmonary inflammation. We hypothesized that MMPs and TIMPs correlate to clinical findings and bronchoalveolar lavage fluid cytology in different equine chronic pneumopathies. Using a scoring system, 61 horses were classified controls as free of respiratory disease (n = 15), recurrent airway obstruction (RAO, n = 17), inflammatory airway disease (IAD, n = 18), or chronic interstitial pneumopathy (CIP, n = 11). Zymography and equine MMP and TIMP assays were used to detect MMP-2, MMP-8, MMP-9 as well as TIMP-1, and TIMP-2 in BALF supernatant. MMP-2, TIMP-1, and TIMP-2 concentrations were significantly increased in RAO and IAD compared to controls. MMP-9 concentration and MMP-8 activity evaluated by fluorimetry were significantly increased in RAO, IAD, and CIP. These results were confirmed by zymography for MMP-2 and MMP-9 activity in 52 horses. In conclusion, MMPs and TIMPs correlate well with clinical and cytologic findings. These findings support the usefulness of MMPs, TIMPs, and their ratios to evaluate the severity of respiratory disease and may help to identify subclinical cases.
Insights
Matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) show altered levels in equine respiratory diseases. These biomarkers correlate with clinical and cytologic findings, aiding in disease severity assessment.
Area of Science:
- Equine medicine
- Pulmonary pathology
- Biomarker discovery
Background:
- Matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) are key regulators of tissue remodeling.
- Imbalances in MMPs and TIMPs are implicated in chronic respiratory diseases, potentially serving as biomarkers.
- Their role in equine pneumopathies requires further investigation to correlate with clinical and cytologic parameters.
Purpose of the Study:
- To investigate the correlation between matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) with clinical and bronchoalveolar lavage fluid (BALF) cytologic findings in horses.
- To evaluate MMPs and TIMPs as potential biomarkers for different equine chronic respiratory conditions.
Main Methods:
- Sixty-one horses were categorized into control, recurrent airway obstruction (RAO), inflammatory airway disease (IAD), and chronic interstitial pneumopathy (CIP) groups.
- Bronchoalveolar lavage fluid (BALF) supernatant was analyzed for MMP-2, MMP-8, MMP-9, TIMP-1, and TIMP-2 using specific assays and zymography.
- Fluorimetry was used to evaluate MMP-8 activity.
Main Results:
- MMP-2, TIMP-1, and TIMP-2 concentrations were elevated in RAO and IAD compared to controls.
- MMP-9 concentration and MMP-8 activity were significantly increased in RAO, IAD, and CIP.
- Zymography confirmed increased MMP-2 and MMP-9 activity in a subset of horses.
Conclusions:
- MMPs and TIMPs levels correlate significantly with clinical signs and cytologic data in equine respiratory diseases.
- These proteinases and their inhibitors are valuable for assessing disease severity and potentially identifying subclinical cases in horses.
- MMP and TIMP profiling offers a promising approach for diagnosing and monitoring equine pulmonary conditions.
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