Determination of free desmosine in human plasma and its application in two experimental medicine studies

Elastin is one of the major extracellular matrix proteins associated with connective tissue. Its degradation leads to the liberation of the unique amino acids desmosine and isodesmosine. These have shown utility as biomarkers of elastin breakdown for disease progression, patient stratification, and...

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Bibliographic Details
Published in:Analytical biochemistry 2013-05, Vol.436 (2), p.127-136
Main Authors: Lamerz, Jens, Friedlein, Arno, Soder, Nicole, Cutler, Paul, Döbeli, Heinz
Format: Article
Language:English
Subjects:
Adult
Age Factors
Aged
amino acids
biomarkers
Biomarkers - blood
Body Mass Index
Body mass index (BMI)
Body Weight
Case-Control Studies
Chemical Precipitation
Chromatography, High Pressure Liquid - methods
Chronic obstructive pulmonary disease (COPD)
Desmosine
Desmosine - blood
Deuterium
disease course
drugs
elastin
ethanol
extracellular matrix
Female
high performance liquid chromatography
Human plasma
Humans
Isodesmosine - blood
Male
mass spectrometry
Mass Spectrometry - methods
medicine
Middle Aged
monitoring
patients
Pulmonary Disease, Chronic Obstructive - blood
Reference Values
Reproducibility of Results
Russia
Selected reaction monitoring (SRM)
Smoking
United States
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Summary:Elastin is one of the major extracellular matrix proteins associated with connective tissue. Its degradation leads to the liberation of the unique amino acids desmosine and isodesmosine. These have shown utility as biomarkers of elastin breakdown for disease progression, patient stratification, and drug efficacy. So far, the quantitation of desmosines in plasma is hampered by complex sample preparation. Here we demonstrate an improved and simplified procedure for detecting both free and total desmosines. The method is based on spiking with a deuterium-labeled desmosine standard, ethanol precipitation, propionylation, high-performance liquid chromatography (HPLC) separation, and selected reaction monitoring (SRM) mass spectrometry. The performance of the assay is illustrated by comparing the levels of free and total desmosines in normal healthy plasma and those from patients diagnosed with chronic obstructive pulmonary disease (COPD). A conserved ratio of 1:3 for free to total desmosine was found. The determination of free desmosine has higher accuracy than that of total desmosine; therefore, it is the method of choice when plasma volume is limiting. Finally, we show that the plasma desmosine concentration correlates with age and body mass index.
ISSN:0003-2697
1096-0309
DOI:10.1016/j.ab.2013.01.012