Lipid mass spectrometry imaging and proteomic analysis of severe aortic stenosis

Severe aortic stenosis (AS) is prevalent in adults ≥ 65 years, a significant cause of morbidity and mortality, with no medical therapy. Lipid and proteomic alterations of human AS tissue were determined using mass spectrometry imaging (MSI) and liquid chromatography electrospray ionization tandem ma...

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Bibliographic Details
Published in:Journal of molecular histology 2020-10, Vol.51 (5), p.559-571
Main Authors: Lim, Jihyeon, Aguilan, Jennifer T., Sellers, Rani S., Nagajyothi, Fnu, Weiss, Louis M., Angeletti, Ruth Hogue, Bortnick, Anna E.
Format: Article
Language:English
Subjects:
Antithrombin
Aortic stenosis
Apolipoproteins
Biomedical and Life Sciences
Biomedicine
Calcification
Cell Biology
Cholesterol
Complement component C3
Complement component C4
Complement factor H
Developmental Biology
Extracellular matrix
Inflammation
Ions
Life Sciences
Lipids
Liquid chromatography
Lysophosphatidylcholine
Mass spectrometry
Mass spectroscopy
Morbidity
Original Paper
Phenotypes
Proteomics
Scientific imaging
Stenosis
Versican
α2-Macroglobulin
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Summary:Severe aortic stenosis (AS) is prevalent in adults ≥ 65 years, a significant cause of morbidity and mortality, with no medical therapy. Lipid and proteomic alterations of human AS tissue were determined using mass spectrometry imaging (MSI) and liquid chromatography electrospray ionization tandem mass spectrometry (LC–ESI–MS/MS) to understand histopathology, potential biomarkers of disease, and progression from non-calcified to calcified phenotype. A reproducible MSI method was developed using healthy murine aortic valves (n = 3) and subsequently applied to human AS (n = 2). Relative lipid levels were spatially mapped and associated with different microdomains. Proteomics for non-calcified and calcified microdomains were performed to ascertain differences in expression. Increased pro-osteogenic and inflammatory lysophosphatidylcholine (LPC) 16:0 and 18:0 were co-localized with calcified microdomains. Proteomics analysis identified differential patterns in calcified microdomains with high LPC and low cholesterol as compared to non-calcified microdomains with low LPC and high cholesterol. Calcified microdomains had higher levels of: apolipoproteins (Apo) B-100 (p 
ISSN:1567-2379
1567-2387
DOI:10.1007/s10735-020-09905-5