Lipid mass spectrometry imaging and proteomic analysis of severe aortic stenosis
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ORIGINAL PAPER
Lipid mass spectrometry imaging and proteomic analysis of severe aortic stenosis Jihyeon Lim1 · Jennifer T. Aguilan2,3 · Rani S. Sellers4 · Fnu Nagajyothi5 · Louis M. Weiss2 · Ruth Hogue Angeletti2,6,7 · Anna E. Bortnick8,9,10 Received: 9 March 2020 / Accepted: 9 August 2020 © Springer Nature B.V. 2020
Abstract 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
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