title: The Role of Arginase 1 in Post-Stroke Immunosuppression and Ischemic Stroke Severity.
abstract: A balanced immune system response plays an important role in acute ischemic stroke (AIS) recovery. Our laboratory has previously identified several immune-related genes, including arginase 1 (ARG1), with altered expression in human AIS patients. The neutrophil-lymphocyte ratio (NLR) may be a marker of the degree of immune dysregulation following AIS; however, the molecular mechanisms that may mediate the NLR are unknown. The purpose of this study was to (1) examine the relationship between ARG1, NLR, and AIS severity and (2) to utilize principal component analysis (PCA) to statistically model multiple gene expression changes following AIS. AIS patients and stroke-free control subjects were recruited, and blood samples were collected from AIS patients within 24 h of stroke symptom onset. White blood cell differentials were obtained at this time to calculate the NLR. Gene expression was measured using real-time PCR. PCA with varimax rotation was used to develop composite variables consisting of a five-gene profile. ARG1 was positively correlated with NLR (r = 0.57, p = 0.003), neutrophil count (r = 0.526, p = 0.007), NIHSS (r = 0.607, p = 0.001), and infarct volume (r = 0.27, p = 0.051). PCA identified three principal components that explain 84.4 % of variation in the original patient gene dataset comprised of ARG1, LY96, MMP9, s100a12, and PC1 was a significant explanatory variable for NIHSS (p < 0.001) and NLR (p = 0.005). Our study suggests a novel relationship between ARG1, NLR, and stroke severity, and the NLR is an underutilized clinically available biomarker to monitor the post-stroke immune response.
authors.affiliation: Department of Neurobiology and Anatomy, West Virginia University, One Medical Center Drive, Morgantown, WV, 26508, USA.|Center for Basic and Translational Stroke Research, West Virginia University, One Medical Center Drive, Erma Byrd 119, Morgantown, WV, 26508, USA.
authors.forename: Ashley B
authors.initials: AB
authors.lastname: Petrone
authors.affiliation: Center for Basic and Translational Stroke Research, West Virginia University, One Medical Center Drive, Erma Byrd 119, Morgantown, WV, 26508, USA.|Department of Pharmaceutical Sciences, West Virginia University, One Medical Center Drive, Morgantown, WV, 26508, USA.
authors.forename: Grant C
authors.initials: GC
authors.lastname: O'Connell
authors.affiliation: Center for Basic and Translational Stroke Research, West Virginia University, One Medical Center Drive, Erma Byrd 119, Morgantown, WV, 26508, USA.|Department of Biostatistics, West Virginia University, One Medical Center Drive, Morgantown, WV, 26508, USA.
authors.forename: Michael D
authors.initials: MD
authors.lastname: Regier
authors.affiliation: Department of Exercise Physiology, West Virginia University, One Medical Center Drive, Morgantown, WV, 26508, USA.|Center for Cardiovascular and Respiratory Sciences, West Virginia University, One Medical Center Drive, Morgantown, WV, 26508, USA.
authors.forename: Paul D
authors.initials: PD
authors.lastname: Chantler
authors.affiliation: Center for Basic and Translational Stroke Research, West Virginia University, One Medical Center Drive, Erma Byrd 119, Morgantown, WV, 26508, USA.|Department of Physiology and Pharmacology, West Virginia University, One Medical Center Drive, Morgantown, WV, 26508, USA.
authors.forename: James W
authors.initials: JW
authors.lastname: Simpkins
authors.affiliation: Center for Basic and Translational Stroke Research, West Virginia University, One Medical Center Drive, Erma Byrd 119, Morgantown, WV, 26508, USA. tlbarr@hsc.wvu.edu.|School of Nursing, West Virginia University, One Medical Center Drive, Morgantown, WV, 26508, USA. tlbarr@hsc.wvu.edu.
authors.forename: Taura L
authors.initials: TL
authors.lastname: Barr
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001119:Arginase / Q000097:blood* / Q000235:genetics; D002545:Brain Ischemia / Q000150:complications; D017364:Collagenases / Q000235:genetics / Q000378:metabolism; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents; D008214:Lymphocytes / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009504:Neutrophils / Q000473:pathology; D025341:Principal Component Analysis; D012333:RNA, Messenger / Q000378:metabolism; D012044:Regression Analysis; D000067616:S100A12 Protein / Q000235:genetics / Q000378:metabolism; D012720:Severity of Illness Index; D020521:Stroke / Q000209:etiology / Q000276:immunology* / Q000378:metabolism / Q000628:therapy*
chemical_list: D007166:Immunosuppressive Agents; D012333:RNA, Messenger; D000067616:S100A12 Protein; C090441:S100A12 protein, human; D017364:Collagenases; C574619:ARG1 protein, human; D001119:Arginase
keywords: Arginase; Immune system; Neutrophil-lymphocyte ratio; Stroke