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

被引:32
|
作者
Wierer, Michael [1 ]
Prestel, Matthias [2 ]
Schiller, Herbert B. [1 ,3 ]
Yan, Guangyao [2 ]
Schaab, Christoph [1 ]
Azghandi, Sepiede [2 ]
Werner, Julia [4 ]
Kessler, Thorsten [4 ]
Malik, Rainer [2 ]
Murgia, Marta [1 ,5 ]
Aherrahrou, Zouhair [6 ,7 ]
Schunkert, Heribert [4 ,8 ]
Dichgans, Martin [2 ]
Mann, Matthias [1 ]
机构
[1] Max Planck Inst Biochem, Dept Prote & Signal Transduct, Klopferspitz 18, D-82152 Martinsried, Germany
[2] Klinikum Univ Munchen, Inst Stroke & Dementia Res, Feodor Lynen Str 17, D-81377 Munich, Germany
[3] German Ctr Lung Res DZL, Comprehens Pneumol Ctr, Helmholtz Zentrum Munchen, Munich, Germany
[4] Tech Univ Munich, Klin Herz & Kreislauferkrankungen, Deutsch Herzzentrum Munchen, Munich, Germany
[5] Univ Padua, Dept Biomed Sci, Padua, Italy
[6] Univ Lubeck, Inst Integrat & Expt Genom, Lubeck, Germany
[7] Deutsch Zentrum Herz Kreislauf Forsch DZHK eV, Partner Site Hamburg Kiel Lubeck, Lubeck, Germany
[8] DZHK eV German Ctr Cardiovasc Res, Partner Site Munich Heart Alliance, Munich, Germany
关键词
SMOOTH-MUSCLE-CELLS; GLOMERULAR EXTRACELLULAR-MATRIX; CORONARY-ARTERY-DISEASE; VASCULAR CALCIFICATION; DEFICIENT MICE; GENE INACTIVATION; IMMUNE-SYSTEM; INFLAMMATION; STROKE; IDENTIFICATION;
D O I
10.1074/mcp.RA117.000315
中图分类号
Q5 [生物化学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
收藏
页码:321 / 334
页数:14
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