Abstract TP161: Differential Expression of PHACTR1 and EDN1 in Atheromatous vs. Normal Carotid Tissue

Abstract

Introduction: Several related neurovascular phenotypes, including cervical artery dissection, fibromuscular dysplasia, large artery stroke, hypertension, and migraine headache are associated with a single nucleotide polymorphism (rs9349378) in the phosphatase and actin regulator-1 ( PHACTR1 ) gene recently identified as a distal regulator of the endothelin-1 ( EDN1 ) gene. Vascular endothelial cells release EDN1, a potent vasoconstrictor. We hypothesize that atheromatous and normal carotid tissue will differentially express PHACTR1 and EDN1 . Methods: We obtained gene expression data from the publically available Gene Expression Omnibus Carotid Atheroma Dataset (GSE43292). This resource contains 32 paired samples of carotid atheroma and distant macroscopically intact carotid tissue from the same individual and gene expression data from the Affymetrix Human Gene 1.0 ST Array. We compared log transformed count of signal intensity of PHACTR1 and EDN1 expression in the 32 paired samples using a two-sample t-test assuming equal variance with SPSS (IBM, Armonk, NY). Results: PHACTR1 expression was lower in atheromatous compared to normal carotid tissue (7.152 vs. 7.399, delta 0.248, 95%CI 0.180 - 0.315, p=1.9 E -8 ). EDN1 expression did not differ (6.514 and 6.339, delta 0.176, 95%CI -0.004 - 0.356, p = 0.055). with genetic data associating the rs9349378[G] allele with lower levels of expression and atherosclerotic vascular diseases. The lack of differential EDN1 expression may reflect the small sample size or may challenge the assertion that EDNI is the mediator of the PHACTR1 association. Our data support the hypothesis that this pathway may play an important and potentially variable role in neurovascular phenotypes including large artery atherosclerotic stroke and non-atherosclerotic arteriopathies.