MassIVE MSV000097042

Partial Public PXD060482

Proteomics reveals spatial and molecular heterogeneities in advanced atherosclerotic carotid artery plaques

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Description

Atherosclerotic plaque rupture is a major cause of cerebrovascular events, yet the molecular determinants underlying vulnerability-related plaque morphology, including fibrous cap thickness, remain incompletely defined. Using histomorphology-guided spatial proteomics, here we delineate molecular programmes associated with plaque cap phenotype across discrete plaque subregions. Across 112 carotid endarterectomy specimens, differences between thin-cap and thick-cap plaques were predominantly localised to the necrotic core and fibrous cap. These differences were enriched for processes related to inflammation, lipid handling, extracellular matrix remodelling, and ossification/calcification, and supported the presence of proteome-based plaque subtypes. PCSK9 was among the proteins most strongly associated with thin-cap plaques. Consistently, an in vitro model of necrotic core-like oxidative and inflammatory stress increased PCSK9 secretion in primary vascular smooth muscle cells. Together, these findings localise molecular programmes associated with cap phenotype to plaque compartments and provide a framework for spatially informed biomarker discovery in advanced carotid atherosclerosis. [doi:10.25345/C5MC8RT94] [dataset license: CC0 1.0 Universal (CC0 1.0)]

Keywords: atherosclerosis ; subregions ; smooth muscle cells ; DatasetType:Proteomics

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Principal Investigators:
(in alphabetical order) 		Matthias Mann, Proteomics and Signal Transduction Max Planck Institute of Biochemistry Am Klopferspitz 18 D-82152 Martinsried, N/A
Submitting User: oroshi
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Distinct protein accessions are counted across all files submitted in the "Statistical Analysis of Quantified Analytes" category having a "Protein" column in this dataset.

"N/A" means no results of this type were submitted.
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