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

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.

SUBMITTER: Wierer M

PROVIDER: S-EPMC5795394 | biostudies-literature | 2018 Feb

REPOSITORIES: biostudies-literature

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

Wierer Michael M Prestel Matthias M Schiller Herbert B HB Yan Guangyao G Schaab Christoph C Azghandi Sepiede S Werner Julia J Kessler Thorsten T Malik Rainer R Murgia Marta M Aherrahrou Zouhair Z Schunkert Heribert H Dichgans Martin M Mann Matthias M

Molecular & cellular proteomics : MCP 20171204 2

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 w ...[more]

PMID: 29208753

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Project description:BackgroundIschemic stroke, which has a high incidence, disability, and mortality rate, is mainly caused by carotid atherosclerotic plaque. The difference in the geometric structures of the carotid arteries inevitably leads to the variability in the local hemodynamics, which plays a key role in the formation of carotid atherosclerosis. At present, the combined mechanisms of hemodynamic and geometric in the formation of carotid atherosclerotic plaque are not clear. Thus, this study characterized the geometric and hemodynamic characteristics of carotid atherosclerotic plaque formation using four-dimensional (4D) flow magnetic resonance imaging (MRI).MethodsUltimately, 122 carotid arteries from 61 patients were examined in this study. According to the presence of plaques at the bifurcation of the carotid artery on cervical vascular ultrasound (US), carotid arteries were placed into a plaque group (N=69) and nonplaque group (N=53). The ratio of the maximum internal carotid artery (ICA) inner diameter to the maximum common carotid artery (CCA) inner diameter (ICA-CCA diameter ratio), bifurcation angle, and tortuosity were measured using neck three-dimensional time-of-flight magnetic resonance angiography (3D TOF-MRA). Meanwhile, 4D flow MRI was used to obtain the following hemodynamic parameters of the carotid arteries: volume flow rate, velocity, wall shear stress (WSS), and pressure gradient (PG). Independent sample t-tests were used to compare carotid artery geometry and hemodynamic changes between the plaque group and nonplaque group.ResultsThe ICA-CCA diameter ratio between the plaque group and the nonplaque group was not significantly different (P=0.124), while there were significant differences in the bifurcation angle (P=0.005) and tortuosity (P=0.032). The bifurcation angle of the plaque group was greater than that of the nonplaque group (60.70°±20.75° vs. 49.32°±22.90°), and the tortuosity was smaller than that of the nonplaque group (1.07±0.04 vs. 1.09±0.05). There were no significant differences between the two groups in terms of volume flow rate (P=0.351) and the maximum value of velocity (velocitymax) (P=0.388), but the axial, circumferential, and 3D WSS values were all significantly different, including their mean values (all P values <0.001) and the maximum value of 3D WSS (P<0.001), with the mean axial, circumferential, 3D WSS values, along with the maximum 3D WSS value, being lower in the plaque group. The two groups also differed significantly in terms of maximum PG value (P=0.030) and mean PG value (P=0.026), with these values being greater in the nonplaque group than in the plaque group.ConclusionsA large bifurcation angle and a low tortuosity of the carotid artery are geometric risk factors for plaque formation in this area. Low WSS and low PG values are associated with carotid atherosclerotic plaque formation.

Dataset Information

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

Publications

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

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