Functional genomics as an emerging strategy for the investigation of central mechanisms in experimental hypertension

Centrally mediated increases in sympathetic nerve activity and attenuated arterial baroreflexes contribute to the pathogenesis of hypertension. Despite the characterization of cellular and physiological mechanisms that regulate blood pressure and alterations that contribute to hypertension, the gene...

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Bibliographic Details
Published in:Progress in Biophysics and Molecular Biology 2004-02, Vol.84 (2), p.107-123
Main Authors: Veerasingham, Shereeni J, Sellers, Kathleen W, Raizada, Mohan K
Format: Article
Language:English
Subjects:
Animals
Brain - pathology
Calmodulin-Binding Proteins - genetics
Gene expression profiles
Gene Expression Regulation
Gene manipulation
Gene Transfer Techniques
Genome
Humans
Hypertension
Intracranial Hypertension - genetics
Intracranial Hypertension - pathology
Neurons - pathology
Oligonucleotide Array Sequence Analysis
Phenotype
Protein transduction and brain
Transgenes
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Summary:Centrally mediated increases in sympathetic nerve activity and attenuated arterial baroreflexes contribute to the pathogenesis of hypertension. Despite the characterization of cellular and physiological mechanisms that regulate blood pressure and alterations that contribute to hypertension, the genetic and molecular basis of this pathophysiology remains poorly understood. Strategies to identify genes that contribute to central pathophysiologic mechanisms in hypertension include integrative biochemistry and physiology as well as functional genomics. This article summarizes recent progress in applying functional genomics to elucidate the genetic basis of altered central blood pressure regulatory mechanisms in hypertension. We describe approaches others and we have undertaken to investigate gene expression profiles in hypertensive models in order to identify genes that contribute to the pathogenesis of hypertension. Finally, we provide the readers a roadmap for negotiating the route from experimental findings of gene expression profiling to translating their therapeutic potential. The combination of gene expression profiling and the phenotypic characterization of in vitro and in vivo loss or gain of function experiments for candidate genes have the potential to identify genes involved in the pathogenesis of hypertension and may present novel targets for therapy.
ISSN:0079-6107
1873-1732
DOI:10.1016/j.pbiomolbio.2003.11.007