Abstract WP114: Alteration in Gene Expression Profiles in Aging Cerebral Cortex Prior to the Occurrence of Stroke in Stroke-Prone Spontaneously Hypertensive Rats

Abstract

Purpose— Stroke is a complex disorder with a poorly understood multifactorial and polygenic etiology. However, little is known about the underlying pathogenic biomarkers. This study was aimed to reveal the antecedent events in the brain of stroke-prone spontaneously hypertensive rats (SHR-SP), by extensive microarray analysis prior to the occurrence of stroke. Method— Blood pressure was measured every week. 0.5% NaCl was loaded everyday from 9 wks of age to promote hypertension additionally. Male SHR-SPs were sacrificed at 6 and 12 wks of age (n=3 and 3, respectively). Wistar-Kyoto rats (WKY; male, 6-wk-old, n=3) utilized as the control sacrificed at 12 wks. Subsequently, total RNA was extracted from cerebral cortices immediately and gene expression profiles were studied using 27k rat cDNA microarray. Differentially expressed probes were determined by one-factor ANOVA (P<0.01). These probes further analyzed with k-means cluster analysis (Number of Clusters: 10). Finally, genes differentially expressed in 12-wk-old SHR-SPs were investigated using the Gene Ontology. Result— All animals did not develop any evidence of stroke symptom. Mean blood pressure was lower than 110 mmHg in all 6-wk-old animals, but gradually elevated up to higher than 180 mmHg only in 12-wk-old SHR-SPs. Extensive microarray analysis identified 414 differentially expressed probes. Of these, k-means cluster analysis revealed 84 probes with significant variance of expression in 12-wk-old SHR-SPs. Of these 84 probes, 39 upregulated and 18 downregulated genes were categorized as recognized genes at NCBI EntrezGene. Gene Ontology analysis of these genes showed no specific patterns. However, this study identified 4 differentially upregulated genes that play an important role in cell growth, cell adhesion, transcription regulation and unknown role, including HtrA serine peptidase 4, periostin, zinc finger protein 189, and oxidation resistance 1. Conclusion— Although further studies are essential to determine the specific roles of these 57 genes in the development of stroke, the present data may provide the first large scale description of alteration in gene expression profiles in SHR-SP and suggest several cues to investigate some biomarkers for cerebral stroke.