In vivo gene transfer and gene modulation in hypertension research.

Transgenic technologies and homologous recombination approaches have been useful for studying the roles of specific genes in systemic hypertension. Recently, we and others have introduced the use of in vivo gene transfer to study the effects of local gene overexpression or inactivation in hypertension. Using in vivo gene transfer for the blood vessel, we have documented the direct hypertrophic action of local angiotensin and the growth-inhibitory effect of nitric oxide. In vivo gene transfer is also an effective method for discovering the unknown functions of a newly cloned gene. Using this approach, we identified the in vivo growth-inhibitory action of the angiotensin II type 2 receptor. In addition, we have developed a novel strategy using transcriptional factor "decoy" oligonucleotides to regulate the interaction of cis- and trans-acting factors involved in the modulation of gene expression in vivo. Thus, the decoy approach can "switch" on or off specific genes in selective tissues in vivo, thereby influencing local gene expression and tissue function. For example, using decoy oligonucleotides, we have "turned on" renin gene expression in the rat liver, in which it is usually not expressed, resulting in increased hepatic and plasma renin levels. Thus, in vivo gene transfer technology provides us with a new tool for in vivo characterization of genes involved in hypertension that has potential application in human therapy.

Duke Scholars

Author Victor J. Dzau Medicine, Cardiology