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 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.
Veerasingham
Shereeni J
SJ
Department of Physiology and Functional Genomics and McKnight Brain Institute, College of Medicine, University of Florida, PO Box 100274, Gainesville, FL 32610, USA.
Sellers
Kathleen W
KW
Raizada
Mohan K
MK
D000818:Animals; D001921:Brain / Q000473:pathology; D002148:Calmodulin-Binding Proteins / Q000235:genetics; D005786:Gene Expression Regulation; D018014:Gene Transfer Techniques; D016678:Genome; D006801:Humans; D019586:Intracranial Hypertension / Q000235:genetics* / Q000473:pathology*; D009474:Neurons / Q000473:pathology; D020411:Oligonucleotide Array Sequence Analysis; D010641:Phenotype; D019076:Transgenes; D000099291:Adducins
D002148:Calmodulin-Binding Proteins; D000099291:Adducins