Proteomic analysis of jugular venous blood in acute large vessel occlusion stroke with futile recanalization

Abstract

Futile recanalization (FR) after endovascular treatment (EVT) remains a significant challenge for acute ischemic stroke (AIS) with large vessel occlusion (LVO). The pathogenesis of FR has not been well elucidated. We prospectively enrolled anterior circulation LVO-AIS patients who achieved successful recanalization after EVT. The jugular venous blood ipsilateral to stroke was collected before and immediately after recanalization. Plasma proteomic analysis based on liquid chromatography-mass spectrometry was performed using data-independent acquisition method. Differentially expressed proteins (DEPs) among patients with or without FR in the whole or propensity score matching (PSM) cohorts were screened according to the absolute value of fold change ≥1.5 and P value <0.05. We identified 104 and 34 DEPs between patients with or without FR in the whole cohort and PSM cohort, respectively. Bioinformatic analysis indicated that the identified proteins were primarily related to specific biological processes including immune response, complement activation, oxidative stress, lipid metabolism, protein ubiquitylation as well as autophagy, suggesting that these may be mechanisms in FR pathogenesis. Collectively, we discovered proteins that may be potential research targets for FR. The combination of proteomic and bioinformatic analysis could provide a better understanding of the pathogenesis of FR in a comprehensive manner.

Keywords: Acute ischemic stroke; futile recanalization; jugular vein; liquid chromatography-mass spectrometry; proteomic analysis.

Figure 1.

The flow diagram of the study.

Figure 2.

The PLS-DA model, volcano plots and heat map of differential proteins of the FR and non-FR (NFR) groups. (a) The PLS-DA model of differential proteins in PreV and PostV plasma samples. Partial separation of the two groups was observed. (b) The volcano plots of the differential proteins in PreV and PostV plasma samples. Red dots in the left X axis (log1.5 (fold change) <-1) represent up-regulated proteins in FR group, in the right X axis (log1.5 (fold change)>1) represent down-regulated proteins in FR group, and dots in gray represent proteins without obvious significant. (c) Heatmap of the differential proteins in PreV and PostV plasma samples.

Figure 3.

GO analysis of the differential proteins in FR and control individuals. (a) Cellular components in PreV and PostV samples. (b) Molecular functions in PreV and PostV samples and (c) Biological processes in PreV and PostV samples.

Figure 4.

KEGG pathway enrichment analysis. The KEGG pathway enrichment analysis for DEPs from the PreV (a), PostV (b), and combination of PreV with PostV (c) plasma samples.