In-Depth AGE and ALE Profiling of Human Albumin in Heart Failure: Ex Vivo Studies

Advanced glycation end-products (AGEs) and advanced lipoxidation end-products (ALEs), particularly carboxymethyl-lysine (CML), have been largely proposed as factors involved in the establishment and progression of heart failure (HF). Despite this evidence, the current literature lacks the comprehens...

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Bibliographic Details
Published in:Antioxidants 2021-02, Vol.10 (3), p.358
Main Authors: Altomare, Alessandra, Baron, Giovanna, Balbinot, Marta, Pedretti, Alessandro, Zoanni, Beatrice, Brioschi, Maura, Agostoni, Piergiuseppe, Carini, Marina, Banfi, Cristina, Aldini, Giancarlo
Format: Article
Language:English
Subjects:
Adducts
advanced glycation end-products (AGEs)
Advanced glycosylation end products
advanced lipoxidation end-products (ALEs)
Age
Albumin
Congestive heart failure
Glycosylation
Health care
Heart failure
Human serum albumin
Lipid peroxidation
Lipids
Lysine
Mass spectrometry
Mass spectroscopy
Oxidative stress
Peptides
Plasma
Proteins
Scientific imaging
Sodium
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Summary:Advanced glycation end-products (AGEs) and advanced lipoxidation end-products (ALEs), particularly carboxymethyl-lysine (CML), have been largely proposed as factors involved in the establishment and progression of heart failure (HF). Despite this evidence, the current literature lacks the comprehensive identification and characterization of the plasma AGEs/ALEs involved in HF (untargeted approach). This work provides the first ex vivo high-resolution mass spectrometry (HR-MS) profiling of AGEs/ALEs occurring in human serum albumin (HSA), the most abundant protein in plasma, characterized by several nucleophilic sites and thus representing the main protein substrate for AGE/ALE formation. A set of AGE/ALE adducts in pooled HF-HSA samples was defined, and a semi-quantitative analysis was carried out in order to finally select those presenting in increased amounts in the HF samples with respect to the control condition. These adducts were statistically confirmed by monitoring their content in individual HF samples by applying a targeted approach. Selected AGEs/ALEs proved to be mostly CML derivatives on Lys residues (i.e., CML-Lys12, CML-Lys378, CML-Lys402), and one deoxy-fructosyl derivative on the Lys 389 (DFK-Lys 389). The nature of CML adducts was finally confirmed using immunological methods and in vitro production of such adducts further confirmed by mass spectrometry.
ISSN:2076-3921
2076-3921
DOI:10.3390/antiox10030358