To test the hypothesis that other similar elastin mutations may predispose to COPD, we screened 90 probands from the Boston Early-Onset COPD Study and 90 smoking control subjects from the Normative Aging Study for mutations in elastin exons using high-resolution DNA melt analysis followed by resequencing.
There is very strong evidence that the integrity of the extracellular matrix, and in particular the elastin fibres, are important in the pathogenesis of COPD.
We postulate that hemizygosity at the elastin gene locus may increase susceptibility towards the development of COPD and emphysema in subjects with WBS.
Thus, using ELISA from elastin peptides, we verified that 43% of the patients with severe early onset of chronic obstructive pulmonary disease tested positive for IgG to elastin in their serum compared to healthy controls.
Versican inhibits assembly of tropoelastin into insoluble elastin and we conclude that the pro-inflammatory phenotype of COPD fibroblasts is not compatible with repair of elastic fibres.
In a multivariable logistic regression analysis adjusted for traditional cardiovascular risk factors and chronic obstructive pulmonary disease, -1306C/T MMP2 (odds ratios [OR] = 0.55 [95% confidence interval, CI .34-.85], P < .007) and G1355AELN (OR = 0.64 ([95% CI .41-.99], P = .046) polymorphisms resulted in independent protective factors for abdominal aortic aneurysm (AAA), whereas 5A/6A MMP3 (OR = 1.82 [95% CI 1.04-3.12], P = .034) and -77 A/G MMP-13 (OR = 2.14 [95% CI 1.18-3.86], P = .012) polymorphisms resulted in independent risk factors for AAA.
Lung tissue sections of chronic models for COPD, either induced by exposure to cigarette smoke, chronic intratracheal lipopolysaccharide instillation, or local tumor necrosis factor (TNF) expression [surfactant protein C (SPC)-TNFα mice], were stained for elastin, collagen, and hyaluronan.
A novel therapy for COPD involving the use of aerosolized hyaluronan (HA) was tested on a small cohort of COPD patients to determine both its safety and efficacy in reducing levels of desmosine and isodesmosine (DID), biomarkers for elastin degradation.
Desmosine and isodesmosine (DID) are unique elastin crosslinks that may serve as biomarkers for elastic fiber degradation in chronic obstructive pulmonary disease.
Versican siRNA treatment reduced versican expression and secretion by pulmonary fibroblasts from both COPD and non-COPD patients (<i>P</i><0.01) and significantly increased deposition of insoluble elastin in the COPD cell cultures (<i>P</i><0.05).
Chronic obstructive pulmonary disease and emphysema are associated with increased elastin peptides (EP) production because of excessive breakdown of lung connective tissue.
I hypothesize that inhibiting elastin calcification by means of magnesium supplementation might counteract both vascular calcification and elastin degradation in COPD.
These data suggest that type VI collagen turnover and elastin degradation by neutrophil elastase are associated with COPD-induced inflammation (eosinophil-bronchitis) and emphysema.
For this reason, the UPEXS has focused on disorders that involve the extracellular matrix in general and elastin specifically, such as pelvic organ prolapse, atrial fibrillation, inguinal hernias, and chronic obstructive pulmonary disease.
Such an agent is hyaluronan aerosol, which is deficient in post mortem lungs with chronic obstructive pulmonary disease and has been shown to block elastin degradation, possibly by a barrier function.
The aim of this study was to explore Th1/Th2 cytokines ratio differences in patients in different stages of COPD and to confirm the hypothesis that elastin exposure might serve as an antigen to initiate the stimulation of CD4 <sup>+</sup> Th1-CXCR3 immune inflammation pathway.
Chronic obstructive pulmonary disease (COPD) and particularly emphysema are characterized by stiffness of the aorta, due in part to accelerated elastin degradation in the lungs and aorta.
Areas covered: We propose inhalation therapy to induce repair of damaged pulmonary elastin fibers by stimulating tropoelastin synthesis, assembly and crosslinking in order to improve lung function in patients with COPD.
Systemic alterations to the synthesis and degradation of elastin may be important to our understanding of disease phenotypes in chronic obstructive pulmonary disease.