Sex Specific Changes in SOD1 Proteomics in Acute Ischemic Stroke

Abstract

IntroductionSuperoxide Dismutase 1 (SOD1) plays an important anti‐oxidant role by destroying free superoxide radicals, and serum levels increase in response to smoking, which is a known risk factor for stroke. The pathology of ischemic stroke includes activation of free radical pathways within the ischemic tissue. Through our previously published Blood and Clot Thrombectomy Registry and Collaboration (BACTRAC) stroke tissue bank (clinicaltrials.gov NCT03153683), we aimed to determine any relationship between intracranial peri‐infarct intraluminal SOD1 proteomics and sex, smoking status, and immediate outcome in stroke patients.MethodsPlasma samples were processed in accordance with the BACTRAC protocol, and underwent Proximity Extension Assay (PEA) via Olink. For each protein, intracranial expression distal to the stroke thrombus was compared to the same subject’s systemic arterial blood as an internal control. Smoking status, and sex difference were analyzed using appropriate two‐way comparisons and regression.Results22 adult subjects (>18yrs) were included in the study, of which 13 (59%) were female. Median age was 64 (24–91). 7 (32%) were active smokers and 5 (23%) had a previous stroke. Mean infarct time was 552 ± 254 minutes and mean infarct volume was 62,361 ± 87,735 mm3. The female population intracranial SOD1 expression was greater in active smokers (p=0.004). No significant change in systemic arterial plasma levels were found in either sex. Moreover, SOD1 intracranial levels adjusted to systemic controls also heeded a sex specific increase in female smokers (p=0.05).ConclusionsSOD1 protein expression was found to be significantly increased in only the intracranial distal‐to‐thrombus blood of females based on smoking status. There were no significant findings of SOD1 expression in the male population. These data suggest that changes in SOD1 expression are acutely sensitive to smoking status, but that such changes are particular to women, emphasizing a major difference in how men and women process stroke pathophysiology.Support or Funding InformationUniversity of Kentucky Center of Clinical and Translational Science