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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

Ratios between collagen degradation and formation at time of exacerbation and at 4 weeks follow-up. Degradation/formation ratio of a collagen type III calculated by serum C3M/Pro-C3, b collagen type IV calculated by serum C4M/P4NP 7S, and c collagen type VI calculated by plasma C6M/Pro-C6. Results are shown as geometric mean with 95 % confidence intervals. Ratios at exacerbation and follow-up were compared using paired t-test. Significance levels: ***P <0.001, ****P <0.0001
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Fig2: Ratios between collagen degradation and formation at time of exacerbation and at 4 weeks follow-up. Degradation/formation ratio of a collagen type III calculated by serum C3M/Pro-C3, b collagen type IV calculated by serum C4M/P4NP 7S, and c collagen type VI calculated by plasma C6M/Pro-C6. Results are shown as geometric mean with 95 % confidence intervals. Ratios at exacerbation and follow-up were compared using paired t-test. Significance levels: ***P <0.001, ****P <0.0001

Mentions: The balance between degradation and formation of collagens was investigated by calculating the ratio between fragments of degradation and formation for collagen types III, IV, and VI (Fig. 2). The mean degradation/formation ratio [95 % CI] was significantly elevated at time of exacerbation for collagen type III (2.33 [2.03–2.66] vs. 1.72 [1.51–1.96], P <0.0001) and collagen type VI (3.61 [2.86–4.56] vs. 2.00 [1.64–2.44], P <0.0001). In contrast, the collagen type IV degradation/formation ratio was 0.18 [0.17–0.20] at exacerbation and increased to 0.20 [0.19–0.22] at follow-up (P = 0.0008).Fig. 2


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)

Ratios between collagen degradation and formation at time of exacerbation and at 4 weeks follow-up. Degradation/formation ratio of a collagen type III calculated by serum C3M/Pro-C3, b collagen type IV calculated by serum C4M/P4NP 7S, and c collagen type VI calculated by plasma C6M/Pro-C6. Results are shown as geometric mean with 95 % confidence intervals. Ratios 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
Show All Figures
getmorefigures.php?uid=PMC4491243&req=5

Fig2: Ratios between collagen degradation and formation at time of exacerbation and at 4 weeks follow-up. Degradation/formation ratio of a collagen type III calculated by serum C3M/Pro-C3, b collagen type IV calculated by serum C4M/P4NP 7S, and c collagen type VI calculated by plasma C6M/Pro-C6. Results are shown as geometric mean with 95 % confidence intervals. Ratios at exacerbation and follow-up were compared using paired t-test. Significance levels: ***P <0.001, ****P <0.0001
Mentions: The balance between degradation and formation of collagens was investigated by calculating the ratio between fragments of degradation and formation for collagen types III, IV, and VI (Fig. 2). The mean degradation/formation ratio [95 % CI] was significantly elevated at time of exacerbation for collagen type III (2.33 [2.03–2.66] vs. 1.72 [1.51–1.96], P <0.0001) and collagen type VI (3.61 [2.86–4.56] vs. 2.00 [1.64–2.44], P <0.0001). In contrast, the collagen type IV degradation/formation ratio was 0.18 [0.17–0.20] at exacerbation and increased to 0.20 [0.19–0.22] at follow-up (P = 0.0008).Fig. 2

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