Intracranial VCAM1 at time of mechanical thrombectomy predicts ischemic stroke severity

Abstract

Background Emergent large vessel occlusion (ELVO) strokes are devastating ischemic vascular events for which novel treatment options are needed. Using vascular cell adhesion molecule 1 (VCAM1) as a prototype, the objective of this study was to identify proteomic biomarkers and network signaling functions that are potential therapeutic targets for adjuvant treatment for mechanical thrombectomy. Methods The blood and clot thrombectomy and collaboration (BACTRAC) study is a continually enrolling tissue bank and registry from stroke patients undergoing mechanical thrombectomy. Plasma proteins from intracranial (distal to clot) and systemic arterial blood (carotid) were analyzed by Olink Proteomics for N=42 subjects. Statistical analysis of plasma proteomics used independent sample t tests, correlations, linear regression, and robust regression models to determine network signaling and predictors of clinical outcomes. Data and network analyses were performed using IBM SPSS Statistics, SAS v 9.4, and STRING V11. Results Increased systemic (p<0.001) and intracranial (p=0.013) levels of VCAM1 were associated with the presence of hypertension. Intracranial VCAM1 was positively correlated to both infarct volume (p=0.032; r=0.34) and edema volume (p=0.026; r=0.35). The %∆ in NIHSS from admittance to discharge was found to be significantly correlated to both systemic (p=0.013; r = −0.409) and intracranial (p=0.011; r = −0.421) VCAM1 levels indicating elevated levels of systemic and intracranial VCAM1 are associated with reduced improvement of stroke severity based on NIHSS from admittance to discharge. STRING-generated analyses identified biologic functional descriptions as well as function-associated proteins from the predictive models of infarct and edema volume. Conclusions The current study provides novel data on systemic and intracranial VCAM1 in relation to stroke comorbidities, stroke severity, functional outcomes, and the role VCAM1 plays in complex protein-protein signaling pathways. These data will allow future studies to develop predictive biomarkers and proteomic targets for drug development to improve our ability to treat a devastating pathology.

Isolation and identification of leukocyte populations in intracranial blood collected during mechanical thrombectomy

“…Five were administered tissue plasminogen activator prior to thrombectomy. According to the National Institutes of Health Stroke Score (NIHSS), on admission 8 subjects had a moderate stroke (NIHSS 5-15), 6 had a moderate/severe stroke (NIHSS [16][17][18][19][20], and 2 had a severe stroke (NIHSS !21). The mean LKN to thrombectomy completion time was 690 AE 393 minutes (one patient's data not reported by physician).…”

“…To date, BACTRAC samples identified within-patient acid-base changes, electrolyte chemistry, and changes in gene and protein expression in intracranial blood with systemic blood as internal comparative controls. 17–20…”

“…To date, BACTRAC samples identified within-patient acid-base changes, electrolyte chemistry, and changes in gene and protein expression in intracranial blood with systemic blood as internal comparative controls. [17][18][19][20] In this study, we set out to investigate how neuroinflammatory responses relate to these previous findings. We started with the established BACTRAC protocol and further developed this protocol to isolate leukocytes for flow cytometry.…”

Long Non-Coding RNA-Mediated Competing Endogenous RNA Networks in Ischemic Stroke: Molecular Mechanisms, Therapeutic Implications, and Challenges

“…Vascular cell adhesion molecule 1 (VCAM1), an endothelial-specific marker, is related to inflammation in cerebrovascular disease ( Maglinger et al, 2021 ; Wang et al, 2021 ). It has been shown that miR-204-5p is a target of VCAM1 and that RMST serves as a ceRNA that regulates VCAM1 expression by sponging miR-204-5p.…”

New Drug Targets to Prevent Death Due to Stroke: A Review Based on Results of Protein-Protein Interaction Network, Enrichment, and Annotation Analyses

“…To promote leukocyte trafficking, the choroid plexus epithelium constitutively expresses intercellular adhesion molecule (ICAM)-1 and VCAM-1, which, together with the mucosal vascular addressin cell-adhesion molecule, are upregulated in stroke [49]. In IS, intracranial VCAM-1 levels are associated with infarct and edema size [93]. Cell-adhesion molecules (CAM) KO models show a reduced infarct size, and administration of anti-CAM antibodies may decrease infarct size [94].…”