Protein signature discovery for ischemic stroke: A pilot study of aortic arch surgery

P0270 

Abstract Submission 

Chris Burke (1), Michael Levitt (1), Michael MacCoss (1), Andy Hoofnagle (1), Christine Wu (1), Theo Bammler (1), James MacDonald (1), Kate Carroll (1), Jonathan Weinstein (1), Scott DeRoo (1)

(1) University of Washington, Seattle, WA

Christopher Burke    -  Contact Me
University of Washington

Michael Levitt    -  Contact Me
University of Washington

Michael MacCoss    -  Contact Me
University of Washington

Andy Hoofnagle    -  Contact Me
University of Washington

Christine Wu    -  Contact Me
University of Washington

Theo Bammler    -  Contact Me
University of Washington

James MacDonald    -  Contact Me
University of Washington

Kate Carroll    -  Contact Me
University of Washington

Jonathan Weinstein    -  Contact Me
University of Washington

Scott DeRoo    -  Contact Me
University of Washington

Christopher Burke    -  Contact Me
University of Washington

Objectives: Ischemic stroke causes time-dependent neuronal injury and is a major public health burden. We developed a novel method for performing ischemic stroke protein signature discovery by analyzing plasma collected during aortic arch surgery with deep hypothermic circulatory arrest (DHCA). This work aims to increase our understanding of stroke during aortic arch surgery as well as identify candidate biomarkers that can be utilized for ischemic stroke diagnosis.

Methods: A total of 21 patients were enrolled (DHCA n=17 and CABG controls n=4). Blood samples were collected at various timepoints during the operation as well as the subsequent hospitalization. All patients underwent post-operative neurologic exam by a trained provider as well as brain MRI. Diffusion weighted imaging (DWI) lesions were volumetrically assessed. Plasma samples were then analyzed by a novel mass spectrometry (MS) technique called Mag-Net, which utilizes an extracellular vesicle enrichment strategy that captures membrane-bound particles from plasma.

Results: Two patients (12%) in the DHCA group had a clinical stroke compared to none of the CABG controls. Fourteen (82%) of DHCA patients had DWI lesions on post-operative MRI compared to 2 (50%) CABG patients. DWI infarct volume was significantly greater in the DHCA group (56 mm3 vs. 3 mm3, p=0.03). A total of 5,376 proteins were identified, 1,125 of which showed a significant difference between paired pre- and post-operative concentrations. Of these, 261 proteins had significantly greater expression among the infarct group as compared to the non-infarct group. Analysis of enrichment pathways of these 261 unique proteins revealed many known stroke pathways (interleukins, FAS, complement pathway, EGF, IGF-1, etc.), providing validation of this methodological approach.

Conclusions: We have developed a novel approach for ischemic stroke protein signature discovery utilizing plasma obtained from patients undergoing aortic arch surgery with DHCA. The results of this preliminary work reveal a distinctive proteomic expression when ischemic infarct occurs in patients undergoing DHCA. Further expansion of this work is needed to better define candidate biomarkers that may be predictive of presence and severity of ischemic stroke. This would increase our understanding of the safety of aortic arch surgery as well as potentially aid in diagnosis of ischemic stroke.

Cerebral Protection