Increased Matrix Metalloproteinase (MMPs) Levels Do Not Predict Disease Severity or Progression in Emphysema

Jeanine M. D'Armiento, Monica P. Goldklang, Andrew A. Hardigan, Patrick Geraghty, Michael D. Roth, John E. Connett, Robert A Wise, Frank C. Sciurba, Steven M. Scharf, Jincy Thankachen, Monirul Islam, Andrew J. Ghio, Robert F. Foronjy

Research output: Contribution to journalArticle

Abstract

Rationale: Though matrix metalloproteinases (MMPs) are critical in the pathogenesis of COPD, their utility as a disease biomarker remains uncertain. This study aimed to determine whether bronchoalveolar lavage (BALF) or plasma MMP measurements correlated with disease severity or functional decline in emphysema. Methods: Enzyme-linked immunosorbent assay and luminex assays measured MMP-1, -9, -12 and tissue inhibitor of matrix metalloproteinase-1 in the BALF and plasma of non-smokers, smokers with normal lung function and moderate-to-severe emphysema subjects. In the cohort of 101 emphysema subjects correlative analyses were done to determine if MMP or TIMP-1 levels were associated with key disease parameters or change in lung function over an 18-month time period. Main Results: Compared to non-smoking controls, MMP and TIMP-1 BALF levels were significantly elevated in the emphysema cohort. Though MMP-1 was elevated in both the normal smoker and emphysema groups, collagenase activity was only increased in the emphysema subjects. In contrast to BALF, plasma MMP-9 and TIMP-1 levels were actually decreased in the emphysema cohort compared to the control groups. Both in the BALF and plasma, MMP and TIMP-1 measurements in the emphysema subjects did not correlate with important disease parameters and were not predictive of subsequent functional decline. Conclusions: MMPs are altered in the BALF and plasma of emphysema; however, the changes in MMPs correlate poorly with parameters of disease intensity or progression. Though MMPs are pivotal in the pathogenesis of COPD, these findings suggest that measuring MMPs will have limited utility as a prognostic marker in this disease.

Original languageEnglish (US)
Article numbere56352
JournalPLoS One
Volume8
Issue number2
DOIs
StatePublished - Feb 18 2013

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Matrix Metalloproteinase 1
Emphysema
metalloproteinases
Matrix Metalloproteinases
disease course
disease severity
Tissue Inhibitor of Metalloproteinase-1
Plasmas
interstitial collagenase
Assays
lung function
Matrix Metalloproteinase 9
Immunosorbents
Chronic Obstructive Pulmonary Disease
Biomarkers
Collagenases
pathogenesis
Lung
gelatinase B
collagenase

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

D'Armiento, J. M., Goldklang, M. P., Hardigan, A. A., Geraghty, P., Roth, M. D., Connett, J. E., ... Foronjy, R. F. (2013). Increased Matrix Metalloproteinase (MMPs) Levels Do Not Predict Disease Severity or Progression in Emphysema. PLoS One, 8(2), [e56352]. https://doi.org/10.1371/journal.pone.0056352

Increased Matrix Metalloproteinase (MMPs) Levels Do Not Predict Disease Severity or Progression in Emphysema. / D'Armiento, Jeanine M.; Goldklang, Monica P.; Hardigan, Andrew A.; Geraghty, Patrick; Roth, Michael D.; Connett, John E.; Wise, Robert A; Sciurba, Frank C.; Scharf, Steven M.; Thankachen, Jincy; Islam, Monirul; Ghio, Andrew J.; Foronjy, Robert F.

In: PLoS One, Vol. 8, No. 2, e56352, 18.02.2013.

Research output: Contribution to journalArticle

D'Armiento, JM, Goldklang, MP, Hardigan, AA, Geraghty, P, Roth, MD, Connett, JE, Wise, RA, Sciurba, FC, Scharf, SM, Thankachen, J, Islam, M, Ghio, AJ & Foronjy, RF 2013, 'Increased Matrix Metalloproteinase (MMPs) Levels Do Not Predict Disease Severity or Progression in Emphysema', PLoS One, vol. 8, no. 2, e56352. https://doi.org/10.1371/journal.pone.0056352
D'Armiento JM, Goldklang MP, Hardigan AA, Geraghty P, Roth MD, Connett JE et al. Increased Matrix Metalloproteinase (MMPs) Levels Do Not Predict Disease Severity or Progression in Emphysema. PLoS One. 2013 Feb 18;8(2). e56352. https://doi.org/10.1371/journal.pone.0056352
D'Armiento, Jeanine M. ; Goldklang, Monica P. ; Hardigan, Andrew A. ; Geraghty, Patrick ; Roth, Michael D. ; Connett, John E. ; Wise, Robert A ; Sciurba, Frank C. ; Scharf, Steven M. ; Thankachen, Jincy ; Islam, Monirul ; Ghio, Andrew J. ; Foronjy, Robert F. / Increased Matrix Metalloproteinase (MMPs) Levels Do Not Predict Disease Severity or Progression in Emphysema. In: PLoS One. 2013 ; Vol. 8, No. 2.
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abstract = "Rationale: Though matrix metalloproteinases (MMPs) are critical in the pathogenesis of COPD, their utility as a disease biomarker remains uncertain. This study aimed to determine whether bronchoalveolar lavage (BALF) or plasma MMP measurements correlated with disease severity or functional decline in emphysema. Methods: Enzyme-linked immunosorbent assay and luminex assays measured MMP-1, -9, -12 and tissue inhibitor of matrix metalloproteinase-1 in the BALF and plasma of non-smokers, smokers with normal lung function and moderate-to-severe emphysema subjects. In the cohort of 101 emphysema subjects correlative analyses were done to determine if MMP or TIMP-1 levels were associated with key disease parameters or change in lung function over an 18-month time period. Main Results: Compared to non-smoking controls, MMP and TIMP-1 BALF levels were significantly elevated in the emphysema cohort. Though MMP-1 was elevated in both the normal smoker and emphysema groups, collagenase activity was only increased in the emphysema subjects. In contrast to BALF, plasma MMP-9 and TIMP-1 levels were actually decreased in the emphysema cohort compared to the control groups. Both in the BALF and plasma, MMP and TIMP-1 measurements in the emphysema subjects did not correlate with important disease parameters and were not predictive of subsequent functional decline. Conclusions: MMPs are altered in the BALF and plasma of emphysema; however, the changes in MMPs correlate poorly with parameters of disease intensity or progression. Though MMPs are pivotal in the pathogenesis of COPD, these findings suggest that measuring MMPs will have limited utility as a prognostic marker in this disease.",
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AU - D'Armiento, Jeanine M.

AU - Goldklang, Monica P.

AU - Hardigan, Andrew A.

AU - Geraghty, Patrick

AU - Roth, Michael D.

AU - Connett, John E.

AU - Wise, Robert A

AU - Sciurba, Frank C.

AU - Scharf, Steven M.

AU - Thankachen, Jincy

AU - Islam, Monirul

AU - Ghio, Andrew J.

AU - Foronjy, Robert F.

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Y1 - 2013/2/18

N2 - Rationale: Though matrix metalloproteinases (MMPs) are critical in the pathogenesis of COPD, their utility as a disease biomarker remains uncertain. This study aimed to determine whether bronchoalveolar lavage (BALF) or plasma MMP measurements correlated with disease severity or functional decline in emphysema. Methods: Enzyme-linked immunosorbent assay and luminex assays measured MMP-1, -9, -12 and tissue inhibitor of matrix metalloproteinase-1 in the BALF and plasma of non-smokers, smokers with normal lung function and moderate-to-severe emphysema subjects. In the cohort of 101 emphysema subjects correlative analyses were done to determine if MMP or TIMP-1 levels were associated with key disease parameters or change in lung function over an 18-month time period. Main Results: Compared to non-smoking controls, MMP and TIMP-1 BALF levels were significantly elevated in the emphysema cohort. Though MMP-1 was elevated in both the normal smoker and emphysema groups, collagenase activity was only increased in the emphysema subjects. In contrast to BALF, plasma MMP-9 and TIMP-1 levels were actually decreased in the emphysema cohort compared to the control groups. Both in the BALF and plasma, MMP and TIMP-1 measurements in the emphysema subjects did not correlate with important disease parameters and were not predictive of subsequent functional decline. Conclusions: MMPs are altered in the BALF and plasma of emphysema; however, the changes in MMPs correlate poorly with parameters of disease intensity or progression. Though MMPs are pivotal in the pathogenesis of COPD, these findings suggest that measuring MMPs will have limited utility as a prognostic marker in this disease.

AB - Rationale: Though matrix metalloproteinases (MMPs) are critical in the pathogenesis of COPD, their utility as a disease biomarker remains uncertain. This study aimed to determine whether bronchoalveolar lavage (BALF) or plasma MMP measurements correlated with disease severity or functional decline in emphysema. Methods: Enzyme-linked immunosorbent assay and luminex assays measured MMP-1, -9, -12 and tissue inhibitor of matrix metalloproteinase-1 in the BALF and plasma of non-smokers, smokers with normal lung function and moderate-to-severe emphysema subjects. In the cohort of 101 emphysema subjects correlative analyses were done to determine if MMP or TIMP-1 levels were associated with key disease parameters or change in lung function over an 18-month time period. Main Results: Compared to non-smoking controls, MMP and TIMP-1 BALF levels were significantly elevated in the emphysema cohort. Though MMP-1 was elevated in both the normal smoker and emphysema groups, collagenase activity was only increased in the emphysema subjects. In contrast to BALF, plasma MMP-9 and TIMP-1 levels were actually decreased in the emphysema cohort compared to the control groups. Both in the BALF and plasma, MMP and TIMP-1 measurements in the emphysema subjects did not correlate with important disease parameters and were not predictive of subsequent functional decline. Conclusions: MMPs are altered in the BALF and plasma of emphysema; however, the changes in MMPs correlate poorly with parameters of disease intensity or progression. Though MMPs are pivotal in the pathogenesis of COPD, these findings suggest that measuring MMPs will have limited utility as a prognostic marker in this disease.

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