Systemic elastin degradation in chronic obstructive pulmonary disease
- John D Maclay1,
- David A McAllister1,
- Roberto Rabinovich1,
- Imran Haq2,
- Scott Maxwell3,
- Stephen Hartland4,
- Martin Connell5,6,
- John T Murchison7,
- Edwin J R van Beek6,
- Robert D Gray4,
- Nicholas L Mills8,
- William MacNee1
- 1ELEGI/Colt Laboratories, Centre for Inflammation Research, University of Edinburgh, Edinburgh, UK
- 2Cambridge Institute for Medical Research, University of Cambridge, Cambridge, UK
- 3Department of Pathology, Royal Infirmary Edinburgh, Edinburgh, UK
- 4Centre for Inflammation Research, University of Edinburgh, Edinburgh, UK
- 5Department of Medical Physics, Royal Infirmary Edinburgh, Edinburgh, UK
- 6Clinical Research Imaging Centre, University of Edinburgh, Edinburgh, UK
- 7Department of Radiology, Royal Infirmary Edinburgh, Edinburgh, UK
- 8BHF/University Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, UK
- Correspondence to Dr John D Maclay, ELEGI Colt Laboratory, Queen's Medical Research Institute, The University of Edinburgh, 47 Little France Crescent, Edinburgh EH16 4TJ, UK;
Contributors Conception and design: JM, DM, NM, RG, WM; Laboratory and radiological methodology and analysis: RR, IH, SM, SH, MC, JM, EvB; Drafting the manuscript for important intellectual content: JM, DM, NM, RG, WM.
- Received 13 August 2011
- Accepted 22 December 2011
- Published Online First 28 February 2012
Background Development of emphysema and vascular stiffness in chronic obstructive pulmonary disease (COPD) may be due to a common mechanism of susceptibility to pulmonary and systemic elastin degradation.
Objectives To investigate whether patients with COPD have evidence of systemic elastin degradation in the skin.
Methods The authors measured cutaneous elastin degradation using immunohistochemistry (percentage area of elastin fibres) in sun-exposed (exposed) and non-sun-exposed (non-exposed) skin biopsies in 16 men with COPD and 15 controls matched for age and cigarette smoke exposure. Quantitative PCR of matrix metalloproteinase (MMP)-2, -9, -12 and tissue inhibitor of metalloproteinase-1 mRNA and zymography for protein expression of MMP-2 and -9 were performed on homogenised skin. Arterial stiffness and emphysema severity were measured using carotid-femoral pulse wave velocity and quantitative CT scanning.
Results Skin elastin degradation was greater in exposed and non-exposed skin of patients with COPD compared with controls (exposed, mean (SD); 43.5 (12.1)% vs 26.3 (6.9)%, p<0.001; non-exposed 22.4 (5.2)% vs 18.1 (4.3)%, p=0.02). Cutaneous expression of MMP-9 mRNA and proMMP-9 concentrations was increased in exposed skin of COPD patients (p=0.004 and p=0.02, respectively) and was also associated with increased skin elastin degradation (r=0.62, p<0.001 and r=0.47, p=0.01, respectively). In the entire cohort of ex-smokers, cutaneous elastin degradation was associated with emphysema severity, FEV1 and pulse wave velocity.
Conclusions Patients with COPD have increased skin elastin degradation compared with controls, which is related to emphysema severity and arterial stiffness. Systemic elastin degradation due to increased proteolytic activity may represent a novel shared mechanism for the pulmonary, vascular and cutaneous features of COPD.
- systemic effects
- COPD mechanisms
- lung proteases
- COPD epidemiology
- COPD exacerbations
- COPD pathology
- oxidative stress
- macrophage biology
- cystic fibrosis
- imaging/CT, MRI, etc
- lung cancer
- primary pulmonary hypertension
- pulmonary embolism
- airway epithelium
- exhaled airway markers
- macrophage biology
- neutrophil biology
Funding This research was funded primarily by a grant from the Scottish Society of Physicians and a Chief Scientist Office Project Grant (CZB/4/424). DM is supported by a Chest, Heart and Stroke Scotland Research Fellowship (R40329). NLM is supported by British Heart Foundation Intermediate Clinical Research Fellowship (FS/10/024).
Competing interests None.
Ethics approval Ethics approval was given by Lothian Regional Ethics Committee.
Provenance and peer review Not commissioned; externally peer reviewed.