Document Detail


Systemic elastin degradation in chronic obstructive pulmonary disease.
MedLine Citation:
PMID:  22374923     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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, 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:
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
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, Non-U.S. Gov't     Date:  2012-02-28
Journal Detail:
Title:  Thorax     Volume:  67     ISSN:  1468-3296     ISO Abbreviation:  Thorax     Publication Date:  2012 Jul 
Date Detail:
Created Date:  2012-06-21     Completed Date:  2012-09-04     Revised Date:  2014-02-20    
Medline Journal Info:
Nlm Unique ID:  0417353     Medline TA:  Thorax     Country:  England    
Other Details:
Languages:  eng     Pagination:  606-12     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
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
Grant Support
ID/Acronym/Agency:
CZB/4/424//Chief Scientist Office; FS/10/024//British Heart Foundation; FS/10/024/28266//British Heart Foundation; G0901697//Medical Research Council
Chemical
Reg. No./Substance:
0/Enzyme Precursors; 0/RNA, Messenger; 9007-58-3/Elastin; EC 3.4.24.-/pro-matrix metalloproteinase 9; EC 3.4.24.35/Matrix Metalloproteinase 9

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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