title: Systemic elastin degradation in chronic obstructive pulmonary disease.
abstract: 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.
  
  
  OBJECTIVE
  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, FEV(1) 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.
authors.affiliation: ELEGI Colt Laboratory, Queen's Medical Research Institute, The University of Edinburgh, 47 Little France Crescent, Edinburgh EH16 4TJ, UK. johnmaclay@gmail.com
authors.forename: John D
authors.initials: JD
authors.lastname: Maclay
authors.forename: David A
authors.initials: DA
authors.lastname: McAllister
authors.forename: Roberto
authors.initials: R
authors.lastname: Rabinovich
authors.forename: Imran
authors.initials: I
authors.lastname: Haq
authors.forename: Scott
authors.initials: S
authors.lastname: Maxwell
authors.forename: Stephen
authors.initials: S
authors.lastname: Hartland
authors.forename: Martin
authors.initials: M
authors.lastname: Connell
authors.forename: John T
authors.initials: JT
authors.lastname: Murchison
authors.forename: Edwin J R
authors.initials: EJ
authors.lastname: van Beek
authors.forename: Robert D
authors.initials: RD
authors.lastname: Gray
authors.forename: Nicholas L
authors.initials: NL
authors.lastname: Mills
authors.forename: William
authors.initials: W
authors.lastname: Macnee
mesh_terms: D000368:Aged; D001706:Biopsy; D018450:Disease Progression; D004549:Elastin / Q000235:genetics* / Q000378:metabolism; D004792:Enzyme Precursors / Q000096:biosynthesis / Q000235:genetics; D005541:Forced Expiratory Volume; D005786:Gene Expression Regulation; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis / Q000235:genetics; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D029424:Pulmonary Disease, Chronic Obstructive / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D012333:RNA, Messenger / Q000235:genetics*; D012129:Respiratory Function Tests; D012867:Skin / Q000378:metabolism* / Q000473:pathology; D012907:Smoking / Q000009:adverse effects / Q000378:metabolism
chemical_list: D004792:Enzyme Precursors; D012333:RNA, Messenger; D004549:Elastin; C120487:pro-matrix metalloproteinase 9; D020780:Matrix Metalloproteinase 9