PROTOMAP analysis of Human Cartoid Plaques
Ontology highlight
ABSTRACT:
INSTRUMENT(S): LTQ Orbitrap Velos, LTQ
ORGANISM(S): Homo Sapiens (human)
TISSUE(S): Heart
SUBMITTER: 
Melissa Dix
LAB HEAD: Benjamin Cravatt
PROVIDER: PXD020405 | Pride | 2020-08-10
REPOSITORIES: Pride
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| 082216_PHU13_01.raw | Raw | |||
| 082216_PHU13_01.sqt | Other | |||
| 082216_PHU13_02.raw | Raw | |||
| 082216_PHU13_02.sqt | Other | |||
| 082216_PHU13_03.raw | Raw |
Items per page: 5 1 - 5 of 440 |
Publications
Parallel Murine and Human Plaque Proteomics Reveals Pathways of Plaque Rupture.
Vaisar Tomáš T Hu Jie H JH Airhart Nathan N Fox Kate K Heinecke Jay J Nicosia Roberto F RF Kohler Ted T Potter Zachary E ZE Simon Gabriel M GM Dix Melissa M MM Cravatt Benjamin F BF Gharib Sina A SA Dichek David A DA
Circulation research 20200730 8
<h4>Rationale</h4>Plaque rupture is the proximate cause of most myocardial infarctions and many strokes. However, the molecular mechanisms that precipitate plaque rupture are unknown.<h4>Objective</h4>By applying proteomic and bioinformatic approaches in mouse models of protease-induced plaque rupture and in ruptured human plaques, we aimed to illuminate biochemical pathways through which proteolysis causes plaque rupture and identify substrates that are cleaved in ruptured plaques.<h4>Methods a ...[more]
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Project description:The rupture of unstable atherosclerotic plaques, leading to debilitating or fatal thrombotic events, is a major health burden worldwide. Limited understanding as to the molecular drivers of plaque instability and rupture hinders efforts in diagnosis and treatment prior to thrombotic events. Utilising an advanced pre-clinical mouse model (Tandem stenosis (TS) model), which presents human-like unstable atherosclerotic disease, we apply high-end omic methods to characterize the molecular signatures associated with plaque instability in atherosclerotic arteries. Through quantitative proteomic profiling, we depict unique proteome signatures of unstable plaques compared to stable plaques and healthy arteries. Coupled with single-cell RNA-sequencing of leukocytes, we describe the heterodimer complex S100a8/S100a9 as unique to unstable plaque, with neutrophils implicated as the transcriptional drivers of S100a8/a9 expression. We confirm S100a9 expression in human carotid atherosclerotic plaques and we further utilise the TS pre-clinical model to pharmacologically inhibit S100a8/S100a9, resulting in plaque stabilisation. Thus, we establish the TS model as a sophisticated translational tool for the profiling of unstable atherosclerotic plaques and demonstrate that unstable and stable atherosclerosis are highly different disease entities.
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2006-01-30 | E-TABM-190 | biostudies-arrayexpress
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