From the Departments of Laboratory Medicine (T.W.K.) and Medicine
(D.G.G.), University of California at San Francisco.
Abstract
Abstract—While the promises of gene
therapy may be years away from realization, the therapeutic use of
drugs that act by modifying gene transcription is a well-established
practice in clinical medicine. Although transcription-modulating drugs
are frequently used in many different specialties, the deliberate
development and use of these agents in cardiovascular
medicine has been comparatively limited. However, research advances in
the area of gene transcription and in the molecular genetic regulation
of blood pressure, insulin resistance, lipid metabolism,
and cell growth are providing new opportunities for controlling the
expression of genes that are relevant to the pathogenesis of
cardiovascular disease and essential hypertension.
These research advances are beginning to converge in the development of
transcription-modulating drugs with the potential to attack genetically
determined risk factors that often cluster in patients with essential
hypertension. Ligand-activated transcription factors that serve
as receptors for small lipophilic compounds such as the
thiazolidinediones and retinoids represent examples of
potential therapeutic targets with direct effects on the expression of
genes relevant to the pathogenesis of essential hypertension and its
complications. Mounting evidence suggesting that the superior
cardiorenal protective properties of converting enzyme
inhibitors are related in part to their ability to
indirectly modify the expression of genes in the heart and vasculature
provides provisional support for the clinical value of this therapeutic
approach. Given the success of transcription-modulating drugs in the
treatment of type II diabetes and many other clinical disorders, it is
anticipated that these agents will be developed as tools for the
prevention and treatment of hypertension and
cardiovascular disease in the not too distant
future.
© 1998 American Heart Association, Inc.
Hypothesis
Transcription-Modulating Drugs
A New Frontier in the Treatment of Essential Hypertension
Key Words: hypertension, essential • genetics • thiazolidinediones • transcription • drugs • blood pressure • angiotensin
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