Abstract P278: Identification of Differentially Expressed Aortic Genes in Brown Norway Introgressed Chromosome 2 Segments into Hypertensive Dahl Salt Sensitive Rats

Abstract

Background: Rat chromosome (RNO) 2 introgression from normotensive Brown Norway (BN) rats into hypertensive Dahl salt sensitive (SS) background (consomic SB2) reduced vascular inflammation. We hypothesized that the BN-RNO2 contains genes that reduce vascular inflammation, which could be identified using microRNA (miRNA) and total RNA expression profiling in aorta of congenic rats containing different portions of BN-RNO2 on the SS background. Methods and Results: Twelve-to-13-week-old male SS rats and congenic rats containing the distal portion of BN-RNO2 (SB2a), the middle segment (SB2b) and the proximal segment (SB2e) on the SS background, fed a normal-salt diet, were studied. Systolic blood pressure (SBP) was measured by telemetry. SBP was lower in SB2a and SB2b but not SB2e compared to SS (125±3, 127±6, 138±4 vs 146±2 mm Hg, P <0.05). Total RNA was extracted from aorta and used to construct libraries for small and total RNA sequencing using Illumina HiSeq-2500. The bioinformatics pipeline included: FastQC for quality control, STAR for genome alignment to Rattus norvegicus release-86, mirdeep2 for miRNA annotation and counting, Htseq-count for mRNA and long non-coding RNA annotation and counting; R for differential expression analysis. Differentially expressed miRNAs and genes (mRNA and non-coding RNA) were identified in SB2a vs SS (miRNAs: 3 up and 2 down, genes: 1 up and 3 down), SB2b vs SS (miRNAs: 2 up and 3 down, genes: 67 up and 112 down) and SB2e vs SS (miRNAs: 29 up and 25 down, genes: 12 up and 35 down), with FDR<0.05. Differentially expressed genes encoded within different BN-RNO2 congenic portions were identified in SB2a vs SS (2 down), SB2b vs SS (14 up and 18 down) and SB2e vs SS (1 down). Conclusions and Perspectives: Differentially expressed BN-RNO2 encoded genes were identified in aorta of congenic SB2a, SB2b and SB2e rats. Whether these genes play a role in inflammation or vascular injury remains to be determined.