Transcriptome profiling and network analysis of genetically hypertensive mice

20 Hypertension is a condition with major cardiovascular and renal complications, affecting 21 nearly a billion patients worldwide. Few validated gene targets are available for 22 pharmacological intervention, so there is a need to identify new biological pathways 23 regulating blood pressure and containing novel targets for treatment. The genetically 24 hypertensive “blood pressure high” (BPH), normotensive “blood pressure normal” 25 (BPN), and hypotensive "blood pressure low" (BPL) inbred mouse strains are an ideal 26 system to study differences in gene expression patterns that may represent such biological 27 pathways. We profiled gene expression in liver, heart, kidney, and aorta from BPH, BPN, 28 and BPL mice and determined which biological processes are enriched in observed 29 organ-specific gene signatures. As a result, we identified multiple biological pathways 30 linked to blood pressure phenotype that could serve as a source of candidate genes causal 31 for hypertension. In order to distinguish in the kidney gene signature genes whose 32 differential expression pattern may cause changes in blood pressure, from those genes 33 whose differential expression pattern results from changes in blood pressure, we 34 integrated phenotype associated genes into Genetic Bayesian networks. The integration 35 of data from gene expression profiling and genetics networks is a valuable approach to 36 identify novel potential targets for the pharmacological treatment of hypertension. 37