Abstract W P100: Arginase-1 Is A Novel Biomarker Of Post-stroke Immune Suppression
Autor: | Taura L Barr, Paul Chantler, Ashley Petrone, Steven Brooks, Jefferson Frisbee, James Simpkins |
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Rok vydání: | 2015 |
Předmět: | |
Zdroj: | Stroke. 46 |
ISSN: | 1524-4628 0039-2499 |
DOI: | 10.1161/str.46.suppl_1.wp100 |
Popis: | Objective: Arginase-1 (ARG1) is a novel biomarker of vascular and immune responses in ischemic stroke (IS). The objective of this study was to determine the relationship between ARG1 peripheral blood gene expression, history of hypertension and IS recovery. Methods: Peripheral blood samples were collected from IS patients’ ≥18 years of age within 24 hours from symptom onset. Stroke severity was determined by the NIHSS. Diagnosis of hypertension and lymphocyte counts were obtained from medical record. Modified rankin scale (MRS) was used to determine 30 day recovery. RNA was extracted from Paxgene RNA tubes, amplified, and hybridized to Illumina HumanRef-8v2 bead chips. Gene expression was compared in a univariate manner between IS patients with good (MRS 0-1) and bad (MRS 2-6) outcome using t-test in GeneSpring. Inflation of type one error was corrected by Bonferroni. Results: Twenty-three IS patients were recruited. Most patients had cardioembolic (n=14; 41.2%) or large artery stroke (n=5; 14.7%). Median pre stroke MRS was 0; median baseline NIHSS was 3 (range 0-24); and median 30 day MRS was 0 (range 0-6). ARG1 was higher in stroke patients with a history of hypertension (p=0.021); and there was an inverse relationship between ARG1 and lymphocyte count. When controlling for age, NIHSS and hypertension, high baseline expression of ARG1 significantly predicted worse scores on the MRS. We conducted a pilot study in n=3 female rats undergoing middle cerebral artery occlusion. As expected, there is an increase in ARG1 expression in the peripheral blood at 2 hours after ischemia that decreases within 24 hours, similar to that which we see in our human IS population. Discussion: This preliminary data supports the hypothesis that mechanisms of ARG1 induced lymphocytopenia are altered by the presence of pre-existing cardiovascular disease and may play a role in post-stroke immune suppression. Future studies are required to determine the functional relationships between ARG1 and immune dysfunction and determine appropriate clinical interventions. |
Databáze: | OpenAIRE |
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