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-myosin heavy chain gene in
hypertensive rodent heart
Department of Physiology and Biophysics, University of California, Irvine, California 92697
The main goal of this study was to examine the
transcriptional activity of different-length
-myosin heavy chain
(
-MHC) promoters in the hypertensive rodent heart using the direct
gene transfer approach. A hypertensive state was induced by abdominal
aortic constriction (AbCon) sufficient to elevate mean arterial
pressure by ~45% relative to control. Results show that
-MHC
promoter activity of all tested wild-type constructs, i.e.,
3500,
408,
299,
215,
171, and
71 bp, was significantly increased in
AbCon hearts. In the normal control hearts, expression of the
71-bp construct was comparable to that of the promoterless vector, but its
induction by AbCon was comparable to that of the other constructs. Additional results, based on mutation analysis and DNA gel mobility shift assays targeting
e1,
e2, GATA, and
e3 elements, show that these previously defined cis-elements in the proximal
promoter are indeed involved in maintaining basal promoter activity;
however, none of these elements, either individually or collectively,
appear to be major players in mediating the hypertension response of the
-MHC gene. Collectively, these results indicate that three separate regions on the
-MHC promoter are involved in the induction of the gene in response to hypertension: 1) a distal region
between
408 and
3500 bp, 2) a proximal region between
299 and
215 bp, and 3) a basal region within
71 bp of
the transcription start site. Future research needs to further
characterize these responsive regions to more fully delineate
-MHC
transcriptional regulation in response to pressure overload.
hypertension; transcription; dual luciferase; in vivo gene transfer
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