Abstract | BACKGROUND: 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.
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Authors | John 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 |
Journal | Thorax
(Thorax)
Vol. 67
Issue 7
Pg. 606-12
(Jul 2012)
ISSN: 1468-3296 [Electronic] England |
PMID | 22374923
(Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Enzyme Precursors
- RNA, Messenger
- Elastin
- pro-matrix metalloproteinase 9
- Matrix Metalloproteinase 9
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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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