Compartment-resolved Proteomic Analysis of Mouse Aorta during Atherosclerotic Plaque Formation Reveals Osteoclast-specific Protein Expression

Michael Wierer, Matthias Prestel, Herbert B. Schiller, Guangyao Yan, Christoph Schaab, Sepiede Azghandi, Julia Werner, Thorsten Kessler, Rainer Malik, Marta Murgia, Zouhair Aherrahrou, Heribert Schunkert, Martin Dichgans, Matthias Mann*

*Korrespondierende/r Autor/-in für diese Arbeit
13 Zitate (Scopus)

Abstract

Atherosclerosis leads to vascular lesions that involve major rearrangements of the vascular proteome, especially of the extracellular matrix (ECM). Using single aortas from ApoE knock out mice, we quantified formation of plaques by single-run, high-resolution mass spectrometry (MS)based proteomics. To probe localization on a proteome-wide scale we employed quantitative detergent solubility profiling. This compartment- and time-resolved resource of atherogenesis comprised 5117 proteins, 182 of which changed their expression status in response to vessel maturation and atherosclerotic plaque development. In the insoluble ECM proteome, 65 proteins significantly changed, including relevant collagens, matrix metalloproteinases and macrophage derived proteins. Among novel factors in atherosclerosis, we identified matrilin-2, the collagen IV crosslinking enzyme peroxidasin as well as the poorly characterized MAM-domain containing 2 (Mamdc2) protein as being up-regulated in the ECM during atherogenesis. Intriguingly, three subunits of the osteoclast specific V-ATPase complex were strongly increased in mature plaques with an enrichment in macrophages thus implying an active de-mineralization function.

OriginalspracheEnglisch
ZeitschriftMolecular and Cellular Proteomics
Jahrgang17
Ausgabenummer2
Seiten (von - bis)321-334
Seitenumfang14
ISSN1535-9476
DOIs
PublikationsstatusVeröffentlicht - 02.2018

Strategische Forschungsbereiche und Zentren

  • Querschnittsbereich: Medizinische Genetik

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