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Accelerated extracellular matrix turnover during exacerbations of COPD.

Sand JM, Knox AJ, Lange P, Sun S, Kristensen JH, Leeming DJ, Karsdal MA, Bolton CE, Johnson SR - Respir. Res. (2015)

Bottom Line: However, the effect on tissue structure and turnover is not well described.Pro-C6 levels were decreased and P4NP 7S levels were elevated during exacerbation (P <0.0001).At time of exacerbation, degradation/formation ratios were increased for collagen types III and VI and decreased for collagen type IV.

View Article: PubMed Central - PubMed

Affiliation: Nordic Bioscience, Biomarkers and Research, Herlev Hovedgade 207, 2730, Herlev, Denmark. jsa@nordicbioscience.com.

ABSTRACT

Background: Exacerbations of chronic obstructive pulmonary disease (COPD) contribute significantly to disease progression. However, the effect on tissue structure and turnover is not well described. There is an urgent clinical need for biomarkers of disease activity associated with disease progression. Extracellular matrix (ECM) turnover reflects activity in tissues and consequently assessment of ECM turnover may serve as biomarkers of disease activity. We hypothesized that the turnover of lung ECM proteins were altered during exacerbations of COPD.

Methods: 69 patients with COPD hospitalised for an exacerbation were recruited at admission and returned for a 4 weeks follow-up. Competitive ELISAs measuring circulating protein fragments in serum or plasma assessed the formation and degradation of collagen types III (Pro-C3 and C3M, respectively), IV (P4NP 7S and C4M, respectively), and VI (Pro-C6 and C6M, respectively), and degradation of elastin (ELM7 and EL-NE) and versican (VCANM).

Results: Circulating levels of C3M, C4M, C6M, ELM7, and EL-NE were elevated during an exacerbation of COPD as compared to follow-up (all P <0.0001), while VCANM levels were decreased (P <0.0001). Pro-C6 levels were decreased and P4NP 7S levels were elevated during exacerbation (P <0.0001). Pro-C3 levels were unchanged. At time of exacerbation, degradation/formation ratios were increased for collagen types III and VI and decreased for collagen type IV.

Conclusions: Exacerbations of COPD resulted in elevated levels of circulating fragments of structural proteins, which may serve as markers of disease activity. This suggests that patients with COPD have accelerated ECM turnover during exacerbations which may be related to disease progression.

No MeSH data available.


Related in: MedlinePlus

Biomarker levels at time of exacerbation and at 4 weeks follow-up. a-f Levels of degradation fragments of collagens type III (serum C3M), IV (serum C4M), and VI (plasma C6M), elastin (serum ELM7 and EL-NE) and versican (plasma VCANM). g-i Levels of fragments released in relation to formation of collagen types III (serum Pro-C3), IV (serum P4NP 7S), and VI (plasma Pro-C6). Results are shown as geometric mean with 95 % confidence intervals. Biomarker levels at exacerbation and follow-up were compared using paired t-test. Significance levels: ***P <0.001, ****P <0.0001
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Fig1: Biomarker levels at time of exacerbation and at 4 weeks follow-up. a-f Levels of degradation fragments of collagens type III (serum C3M), IV (serum C4M), and VI (plasma C6M), elastin (serum ELM7 and EL-NE) and versican (plasma VCANM). g-i Levels of fragments released in relation to formation of collagen types III (serum Pro-C3), IV (serum P4NP 7S), and VI (plasma Pro-C6). Results are shown as geometric mean with 95 % confidence intervals. Biomarker levels at exacerbation and follow-up were compared using paired t-test. Significance levels: ***P <0.001, ****P <0.0001

Mentions: Circulating levels of protein fragments released at time of exacerbation and at a clinically stable disease period at 4 weeks follow-up are presented in Table 3. Degradation fragments of collagen type III (C3M), collagen type IV (C4M), collagen type VI (C6M), and elastin (ELM7 and EL-NE) were significantly elevated at exacerbation compared to follow-up (all P <0.0001; Fig. 1a-e). In contrast, a fragment of versican degradation (VCANM) showed a significantly decreased mean level at time of exacerbation (P <0.0001; Fig. 1f). Levels of fragments related to protein formation were not significantly changed for collagen type III (Pro-C3), but were increased for collagen type IV (P4NP 7S; P <0.0001) and decreased for collagen type VI (Pro-C6; P <0.0001) at exacerbation compared to follow-up (Fig. 1g-i). To investigate the effect of smoking on circulating levels of protein fragments, analysis was performed on current and ex smokers, individually, with similar results (data not shown).Table 3


Accelerated extracellular matrix turnover during exacerbations of COPD.

Sand JM, Knox AJ, Lange P, Sun S, Kristensen JH, Leeming DJ, Karsdal MA, Bolton CE, Johnson SR - Respir. Res. (2015)

Biomarker levels at time of exacerbation and at 4 weeks follow-up. a-f Levels of degradation fragments of collagens type III (serum C3M), IV (serum C4M), and VI (plasma C6M), elastin (serum ELM7 and EL-NE) and versican (plasma VCANM). g-i Levels of fragments released in relation to formation of collagen types III (serum Pro-C3), IV (serum P4NP 7S), and VI (plasma Pro-C6). Results are shown as geometric mean with 95 % confidence intervals. Biomarker levels at exacerbation and follow-up were compared using paired t-test. Significance levels: ***P <0.001, ****P <0.0001
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
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getmorefigures.php?uid=PMC4491243&req=5

Fig1: Biomarker levels at time of exacerbation and at 4 weeks follow-up. a-f Levels of degradation fragments of collagens type III (serum C3M), IV (serum C4M), and VI (plasma C6M), elastin (serum ELM7 and EL-NE) and versican (plasma VCANM). g-i Levels of fragments released in relation to formation of collagen types III (serum Pro-C3), IV (serum P4NP 7S), and VI (plasma Pro-C6). Results are shown as geometric mean with 95 % confidence intervals. Biomarker levels at exacerbation and follow-up were compared using paired t-test. Significance levels: ***P <0.001, ****P <0.0001
Mentions: Circulating levels of protein fragments released at time of exacerbation and at a clinically stable disease period at 4 weeks follow-up are presented in Table 3. Degradation fragments of collagen type III (C3M), collagen type IV (C4M), collagen type VI (C6M), and elastin (ELM7 and EL-NE) were significantly elevated at exacerbation compared to follow-up (all P <0.0001; Fig. 1a-e). In contrast, a fragment of versican degradation (VCANM) showed a significantly decreased mean level at time of exacerbation (P <0.0001; Fig. 1f). Levels of fragments related to protein formation were not significantly changed for collagen type III (Pro-C3), but were increased for collagen type IV (P4NP 7S; P <0.0001) and decreased for collagen type VI (Pro-C6; P <0.0001) at exacerbation compared to follow-up (Fig. 1g-i). To investigate the effect of smoking on circulating levels of protein fragments, analysis was performed on current and ex smokers, individually, with similar results (data not shown).Table 3

Bottom Line: However, the effect on tissue structure and turnover is not well described.Pro-C6 levels were decreased and P4NP 7S levels were elevated during exacerbation (P <0.0001).At time of exacerbation, degradation/formation ratios were increased for collagen types III and VI and decreased for collagen type IV.

View Article: PubMed Central - PubMed

Affiliation: Nordic Bioscience, Biomarkers and Research, Herlev Hovedgade 207, 2730, Herlev, Denmark. jsa@nordicbioscience.com.

ABSTRACT

Background: Exacerbations of chronic obstructive pulmonary disease (COPD) contribute significantly to disease progression. However, the effect on tissue structure and turnover is not well described. There is an urgent clinical need for biomarkers of disease activity associated with disease progression. Extracellular matrix (ECM) turnover reflects activity in tissues and consequently assessment of ECM turnover may serve as biomarkers of disease activity. We hypothesized that the turnover of lung ECM proteins were altered during exacerbations of COPD.

Methods: 69 patients with COPD hospitalised for an exacerbation were recruited at admission and returned for a 4 weeks follow-up. Competitive ELISAs measuring circulating protein fragments in serum or plasma assessed the formation and degradation of collagen types III (Pro-C3 and C3M, respectively), IV (P4NP 7S and C4M, respectively), and VI (Pro-C6 and C6M, respectively), and degradation of elastin (ELM7 and EL-NE) and versican (VCANM).

Results: Circulating levels of C3M, C4M, C6M, ELM7, and EL-NE were elevated during an exacerbation of COPD as compared to follow-up (all P <0.0001), while VCANM levels were decreased (P <0.0001). Pro-C6 levels were decreased and P4NP 7S levels were elevated during exacerbation (P <0.0001). Pro-C3 levels were unchanged. At time of exacerbation, degradation/formation ratios were increased for collagen types III and VI and decreased for collagen type IV.

Conclusions: Exacerbations of COPD resulted in elevated levels of circulating fragments of structural proteins, which may serve as markers of disease activity. This suggests that patients with COPD have accelerated ECM turnover during exacerbations which may be related to disease progression.

No MeSH data available.


Related in: MedlinePlus