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.

Association mapping of blood pressure levels in a longitudinal framework using binomial regression

“…The RNA expression in PTPRG has been reported to be upregulated for arrhythmogenic right ventricular cardiomyopathy in humans [7]. On the other hand, the RNA expression of FHIT is downregulated in mouse for low blood pressure [8]. Although we obtain only one association finding that satisfies the genome-wide FDR threshold of 0.05, it is likely that the sample size is grossly inadequate to detect associations for a complex phenotype.…”

Transcriptome profiling reveals that the SM22α-regulated molecular pathways contribute to vascular pathology

“…The expression of SM22α is down-regulated in vascular diseases including atherosclerosis [12], abdominal aortic aneurysms [13] and hypotension [14]. Moreover, decreased expression of SM22α has been widely reported in many solid tumors, such as breast cancer [15], prostate cancer [16] and colorectal cancer [17], which may be an important early event of angiogenesis in tumor progression.…”

Post-Transcriptional Regulation of Renalase Gene by miR-29 and miR-146 MicroRNAs: Implications for Cardiometabolic Disorders

“…hypertensive BPH, normotensive blood pressure normal (BPN) and hypotensive BPL] has been reported to be − 1.0636-fold (p = 0.6548) for BPH as compared to BPN and 1.3763-fold (p = 0.02063) for BPL as compared to BPN, indicating~1.3-fold lower expression in BPH than BPL [29]. Consistently, the renalase mRNA and protein levels were diminished in BPH kidney tissues (by~1.6-fold and~1.8-fold, respectively, as compared to BPL) (Fig.…”