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Systemic elastin degradation in chronic obstructive pulmonary disease.

AbstractBACKGROUND:
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, 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.
AuthorsJohn D Maclay, David A McAllister, Roberto Rabinovich, Imran Haq, Scott Maxwell, Stephen Hartland, Martin Connell, John T Murchison, Edwin J R van Beek, Robert D Gray, Nicholas L Mills, William Macnee
JournalThorax (Thorax) Vol. 67 Issue 7 Pg. 606-12 (Jul 2012) ISSN: 1468-3296 [Electronic] England
PMID22374923 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Enzyme Precursors
  • RNA, Messenger
  • Elastin
  • pro-matrix metalloproteinase 9
  • Matrix Metalloproteinase 9
Topics
  • Aged
  • Biopsy
  • Disease Progression
  • Elastin (genetics, metabolism)
  • Enzyme Precursors (biosynthesis, genetics)
  • Forced Expiratory Volume
  • Gene Expression Regulation
  • Humans
  • Immunohistochemistry
  • Male
  • Matrix Metalloproteinase 9 (biosynthesis, genetics)
  • Middle Aged
  • Polymerase Chain Reaction
  • Pulmonary Disease, Chronic Obstructive (genetics, metabolism, physiopathology)
  • RNA, Messenger (genetics)
  • Respiratory Function Tests
  • Skin (metabolism, pathology)
  • Smoking (adverse effects, metabolism)

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