title: Transcriptome profiling and network analysis of genetically hypertensive mice identifies potential pharmacological targets of hypertension.
abstract: Hypertension is a condition with major cardiovascular and renal complications, affecting nearly a billion patients worldwide. Few validated gene targets are available for pharmacological intervention, so there is a need to identify new biological pathways regulating blood pressure and containing novel targets for treatment. The genetically hypertensive "blood pressure high" (BPH), normotensive "blood pressure normal" (BPN), and hypotensive "blood pressure low" (BPL) inbred mouse strains are an ideal system to study differences in gene expression patterns that may represent such biological pathways. We profiled gene expression in liver, heart, kidney, and aorta from BPH, BPN, and BPL mice and determined which biological processes are enriched in observed organ-specific signatures. As a result, we identified multiple biological pathways linked to blood pressure phenotype that could serve as a source of candidate genes causal for hypertension. To distinguish in the kidney signature genes whose differential expression pattern may cause changes in blood pressure from those genes whose differential expression pattern results from changes in blood pressure, we integrated phenotype-associated genes into Genetic Bayesian networks. The integration of data from gene expression profiling and genetics networks is a valuable approach to identify novel potential targets for the pharmacological treatment of hypertension.
authors.affiliation: Department of Molecular Profiling Research Informatics, Merck Research Laboratories, Rahway, New Jersey 07065, USA.
authors.forename: Oscar
authors.initials: O
authors.lastname: Puig
authors.forename: I-Ming
authors.initials: IM
authors.lastname: Wang
authors.forename: Ping
authors.initials: P
authors.lastname: Cheng
authors.forename: Pris
authors.initials: P
authors.lastname: Zhou
authors.forename: Sophie
authors.initials: S
authors.lastname: Roy
authors.forename: Doris
authors.initials: D
authors.lastname: Cully
authors.forename: Mette
authors.initials: M
authors.lastname: Peters
authors.forename: Yair
authors.initials: Y
authors.lastname: Benita
authors.forename: John
authors.initials: J
authors.lastname: Thompson
authors.forename: Tian-Quan
authors.initials: TQ
authors.lastname: Cai
mesh_terms: D000818:Animals; D001011:Aorta / Q000378:metabolism; D001794:Blood Pressure / Q000235:genetics; D004195:Disease Models, Animal; D020869:Gene Expression Profiling; D006973:Hypertension / Q000235:genetics*; D007668:Kidney / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D008954:Models, Biological; D009206:Myocardium / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis