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The European Respiratory Journal Apr 2012
Topics: Desmosine; Female; Humans; Isodesmosine; Lung; Male; Pulmonary Disease, Chronic Obstructive
PubMed: 22467719
DOI: 10.1183/09031936.00172911 -
Frontiers in Medicine 2023Developing an effective treatment for pulmonary emphysema will require a better understanding of the molecular changes responsible for distention and rupture of alveolar...
Developing an effective treatment for pulmonary emphysema will require a better understanding of the molecular changes responsible for distention and rupture of alveolar walls. A potentially useful approach to studying this process involves the concept of emergence in which interactions at different levels of scale induce a phase transition comprising a spontaneous reorganization of chemical and physical systems. Recent studies in our laboratory provide evidence of this phenomenon in pulmonary emphysema by relating the emergence of airspace enlargement to the release of elastin-specific desmosine and isodesmosine (DID) crosslinks from damaged elastic fibers. When the mean alveolar diameter exceeded 400 μm, the level of peptide-free DID in human lungs was greatly increased, reflecting rapid acceleration of elastin breakdown, alveolar wall rupture, and a phase transition to an active disease state that is less responsive to treatment. Based on this finding, it is hypothesized that free DID in urine and other body fluids may serve as a biomarker for early detection of airspace enlargement, thereby facilitating timely therapeutic intervention and reducing the risk of respiratory failure.
PubMed: 38164218
DOI: 10.3389/fmed.2023.1322283 -
Connective Tissue Research 1980A radioimmunoassay was developed for the determination of desmosine. Desmosine conjugated to albumin was injected into rabbits which developed useful titers of serum...
A radioimmunoassay was developed for the determination of desmosine. Desmosine conjugated to albumin was injected into rabbits which developed useful titers of serum antibodies after six months. A radioactive probe was prepared with desmosine using [125I]-Bolton-Hunter reagent. Bound desmosine was separated from free desmosine by cellulose acetate filter binding. The sensitivity of the assay is 1-50 picomoles of desmosine. The antibody is highly selective for desmosine, reacting less than 1% with other known crosslinks. Some prepurification may be necessary with complex samples which contain trace amounts of elastin peptides.
Topics: Albumins; Amino Acids; Animals; Antibody Specificity; Cattle; Cricetinae; Desmosine; Elastin; Humans; Microchemistry; Rabbits; Radioimmunoassay
PubMed: 6450027
DOI: 10.3109/03008208009152362 -
Frontiers in Cardiovascular Medicine 2022Elastin degradation is implicated in the pathology of vulnerable plaque. Recent studies show promising results for plasma desmosine (pDES), an elastin-specific...
BACKGROUND
Elastin degradation is implicated in the pathology of vulnerable plaque. Recent studies show promising results for plasma desmosine (pDES), an elastin-specific degradation product, as a marker of cardiovascular disease (CVD) outcomes. The aim of this study was to investigate the potential role of pDES as a marker of clinical outcome in patients with acute myocardial infarction (AMI).
MATERIALS AND METHODS
In this case-control study, we studied 236 AMI patients: 79 patients who had death and/or myocardial infarction (MI) at 2 years, and 157 patients who did not have an event at 2 years. pDES was measured using a validated liquid chromatography-tandem mass spectrometry method. Association of pDES with adverse outcomes, and the incremental value of pDES to global registry of acute coronary events (GRACE) score for risk stratification was assessed.
RESULTS
pDES levels were elevated in patients with the composite outcome of death/MI at 2 years ( = 0.002). Logistic regression analyses showed pDES to be associated with death/MI at 2 years [Odds ratio (OR) 5.99 (95% CI 1.81-19.86) = 0.003]. pDES remained a significant predictor of death/MI at 2 years even after adjustment for age, sex, history of CVD, revascularisation, blood pressure, medications on discharge, Troponin I, and NT-proBNP levels.[OR 5.60 (95% CI 1.04-30.04) = 0.044]. In another multivariable model including adjustment for eGFR, pDES was significantly associated with the composite outcome at 6 months, but not at 2 years follow up. DES was also able to reclassify risk stratification for death/MI at 6 months, when added to the GRACE risk model [Net Reclassification Index (NRI) 41.2 (95% CI 12.0-70.4) = 0.006].
CONCLUSION
pDES concentrations predict clinical outcomes in patients with AMI, demonstrating its potential role as a prognostic marker in AMI.
PubMed: 36479574
DOI: 10.3389/fcvm.2022.992388 -
Journal of the American Heart... Oct 2019Background It is recognized that factors beyond aortic size are important in predicting outcome in abdominal aortic aneurysm (AAA) disease. AAA is characterized by the... (Observational Study)
Observational Study
Background It is recognized that factors beyond aortic size are important in predicting outcome in abdominal aortic aneurysm (AAA) disease. AAA is characterized by the breakdown of elastin within the aortic tunica media, leading to aortic dilatation and rupture. The aim of this study was to investigate the association of plasma desmosine (pDES), an elastin-specific degradation product, with disease severity and clinical outcome in patients with AAA. Methods and Results We measured pDES and serum biomarker concentrations in 507 patients with AAAs (94% men; mean age, 72.4±6.1 years; mean AAA diameter, 48±8 mm) and 162 control subjects (100% men; mean age, 71.5±4.4 years) from 2 observational cohort studies. In the longitudinal cohort study (n=239), we explored the incremental prognostic value of pDES on AAA events. pDES was higher in patients with AAA compared with control subjects (mean±SD: 0.46±0.22 versus 0.33±0.16 ng/mL; <0.001) and had the strongest correlation with AAA diameter (=0.39; <0.0001) of any serum biomarker. After adjustment for baseline AAA diameter, pDES was associated with an AAA event (hazard ratio, 2.03 per SD increase [95% CI, 1.02-4.02]; =0.044). In addition to AAA diameter, pDES provided incremental improvement in risk stratification (continuous net reclassification improvement, 34.4% [95% CI, -10.8% to 57.5%; =0.09]; integrated discrimination improvement, 0.04 [95% CI, 0.00-0.15; =0.050]). Conclusions pDES concentrations predict disease severity and clinical outcomes in patients with AAA. Clinical Trial Registration http://www.isrctn.com. Unique identifier: ISRCTN76413758.
Topics: Aged; Aorta, Abdominal; Aortic Aneurysm, Abdominal; Biomarkers; Cardiac Catheterization; Desmosine; Female; Follow-Up Studies; Humans; Incidence; Male; Prognosis; Prospective Studies; Survival Rate; Ultrasonography; United Kingdom
PubMed: 31595818
DOI: 10.1161/JAHA.119.013743 -
Journal of the American Society For... May 2015Elastin is a vital protein of the extracellular matrix of jawed vertebrates and provides elasticity to numerous tissues. It is secreted in the form of its soluble...
Elastin is a vital protein of the extracellular matrix of jawed vertebrates and provides elasticity to numerous tissues. It is secreted in the form of its soluble precursor tropoelastin, which is subsequently cross-linked in the course of the elastic fiber assembly. The process involves the formation of the two tetrafunctional amino acids desmosine (DES) and isodesmosine (IDES), which are unique to elastin. The resulting high degree of cross-linking confers remarkable properties, including mechanical integrity, insolubility, and long-term stability to the protein. These characteristics hinder the structural elucidation of mature elastin. However, MS(2) data of linear and cross-linked peptides released by proteolysis can provide indirect insights into the structure of elastin. In this study, we performed energy-resolved collision-induced dissociation experiments of DES, IDES, their derivatives, and DES-/IDES-containing peptides to determine characteristic product ions. It was found that all investigated compounds yielded the same product ion clusters at elevated collision energies. Elemental composition determination using the exact masses of these ions revealed molecular formulas of the type CxHyN, suggesting that the pyridinium core of DES/IDES remains intact even at relatively high collision energies. The finding of these specific product ions enabled the development of a similarity-based scoring algorithm that was successfully applied on LC-MS/MS data of bovine elastin digests for the identification of DES-/IDES-cross-linked peptides. This approach facilitates the straightforward investigation of native cross-links in elastin.
Topics: Animals; Cattle; Chromatography, High Pressure Liquid; Cross-Linking Reagents; Desmosine; Elastin; Humans; Isodesmosine; Models, Molecular; Molecular Structure; Molecular Weight; Oligopeptides; Peptide Fragments; Peptide Mapping; Protein Stability; Proteolysis; Spectrometry, Mass, Electrospray Ionization; Stereoisomerism; Tandem Mass Spectrometry; Tropoelastin
PubMed: 25604393
DOI: 10.1007/s13361-014-1075-9 -
Experimental Eye Research Feb 2022Pseudoexfoliation syndrome (PXF) is an idiopathic disease with a high prevalence rate. The elastosis disorder is contributed by genetic and non-genetic factors. Elastin...
Pseudoexfoliation syndrome (PXF) is an idiopathic disease with a high prevalence rate. The elastosis disorder is contributed by genetic and non-genetic factors. Elastin dysregulation associated with the disease mechanism is incompletely understood. This study evaluated the molecules of the elastogenesis machinery in PXF. Lens capsule and aqueous humor (aqH) samples (age/sex-matched) were collected from the eyes with PXF alone and PXF with glaucoma (PXF-G) undergoing Extra Capsular Cataract Extraction (ECCE) surgery. The Elastin turnover was assessed by estimating Desmosine levels in the lens capsules by HPLC analysis. Expression of elastogenesis genes [EMILIN1, CLU, FBN1, FN1, FBLN5, FBLN4 and LOXL1] were evaluated in the lens capsule by qPCR while the proteins were assessed in aqH by western blot analysis. The Desmosine content in the lens capsules were 3-fold and 6-fold elevated in PXF (P = 0.02) and PXF-G (P = 0.01) respectively compared to the cataract-alone, indicating increased elastin degradation. A significant increase in the transcript levels of the CLU, FBLN4, EMILIN1, FBLN5, FN1, FBN1, LOXL1 along with significant changes in protein expression of CLU, FBLN5, FBN1 and LOXL1 signified up-regulation of the elastogenesis machinery. The study provides direct evidence of augmented elastin degradation and turnover in the lens capsule of PXF marked by increased Desmosine content and the expression of proteins involved in mature elastin formation.
Topics: Capsules; Cataract; Desmosine; Elastin; Exfoliation Syndrome; Glaucoma; Humans; Lens Capsule, Crystalline
PubMed: 34929161
DOI: 10.1016/j.exer.2021.108898 -
ERJ Open Research May 2023https://bit.ly/4015xZ9.
https://bit.ly/4015xZ9.
PubMed: 37377655
DOI: 10.1183/23120541.00078-2023 -
Biomarkers : Biochemical Indicators of... Jun 2022Desmosine and isodesmosine (DID) are biomarkers for elastic fibre damage in pulmonary emphysema. However, current methods for measuring lung DID involve tissue...
INTRODUCTION
Desmosine and isodesmosine (DID) are biomarkers for elastic fibre damage in pulmonary emphysema. However, current methods for measuring lung DID involve tissue hydrolysis and lack specificity for those fibres undergoing breakdown. To address this limitation, free (nonpeptide-bound) DID content in unhydrolyzed tissues was evaluated as a more accurate biomarker in an animal model of pulmonary emphysema.
METHODS
Hamsters were treated with either cigarette smoke and lipopolysaccharide (LPS), room air and LPS, or room air alone (controls). Free DID levels in fresh and formalin-fixed lungs were measured by LC-MS/MS and correlated with the mean linear intercept (MLI) measure of airspace size.
RESULTS
There was no significant difference in free DID between fresh and formalin-fixed lungs. Animals treated with smoke and LPS had significantly higher levels of free DID than the LPS only group (359 vs. 93.1 ng/g wet lung, respectively; = 0.0012) and room air controls (undetectable levels; = 0.0002). There was a significant positive correlation between free DID and MLI ( < 0.0001).
CONCLUSIONS
The results support the hypothesis that free lung DID is a sensitive indicator of alveolar wall injury that may be used to study the development of pulmonary emphysema in both animal models and post-mortem human lung tissue.
Topics: Animals; Biomarkers; Bronchoalveolar Lavage Fluid; Chromatography, Liquid; Cricetinae; Desmosine; Elastic Tissue; Formaldehyde; Humans; Isodesmosine; Lipopolysaccharides; Lung; Pulmonary Emphysema; Tandem Mass Spectrometry
PubMed: 35170389
DOI: 10.1080/1354750X.2022.2043443 -
American Journal of Respiratory and... Sep 2020
Topics: Aged; Biomarkers; Bronchiectasis; Cardiovascular Diseases; Cause of Death; Desmosine; Female; Humans; Male; Middle Aged
PubMed: 32402210
DOI: 10.1164/rccm.202002-0434LE