Ischemic Stroke Thrombus Perviousness Is Associated with Distinguishable Proteomic Features and Susceptibility to ADAMTS13-Augmented Thrombolysis.

Publication/Presentation Date

12-29-2023

Abstract

BACKGROUND AND PURPOSE: Perviousness is the differential attenuation on CT of an intracranial arterial occlusive thrombus before and after IV contrast administration. While perviousness/permeability has been shown to be related to various clinical outcomes and reflects histopathologic composition, it remains unclear whether perviousness is also associated with differences in proteomic composition.

MATERIALS AND METHODS: Retrieved clots from 59 patients were evaluated with quantitative mass spectrometry. Proteomic differences between high-perviousness (≥11 HU) and low-perviousness (< 11 HU) clots were investigated. Perviousness as a continuous variable was also correlated with protein abundance. Last, an ex vivo lysis assay was performed to investigate the differential susceptibility to tPA, deoxyribonuclease, and ADAMTS13 thrombolysis as a function of perviousness.

RESULTS: In total, 2790 distinct proteins were identified. Thrombus perviousness was associated with distinct proteomic features, including depletion of the macrophage marker CD14 (

CONCLUSIONS: Thrombus perviousness is associated with complex proteomic features, including differential abundance of platelet-related proteins in highly permeable clots with monocyte/macrophage depletion. This association may help to explain why highly pervious thrombi were also found more susceptible to ADAMTS13-augmented thrombolysis.

Volume

45

Issue

1

First Page

22

Last Page

29

ISSN

1936-959X

Disciplines

Medicine and Health Sciences

PubMedID

38123915

Department(s)

Department of Surgery

Document Type

Article

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