一氧化氮合成酵素及過氧化氫酵素基因經由腺病毒媒介傳送入心臟細胞對內皮素所誘發細胞肥大的抑制作用

Cardiomyocyte hypertrophy play a
transition step in the pathogenesis of heart
failure. The objectives of this study were to
determine whether transfer of recombinant
endothelial nitric oxide synthase (eNOS)
gene to neonatal rat cardiomyocytes would
result in expression of a functional enzyme
and to assess the effect of expression of
eNOS on cardiomyocyte hypertrophy.
Cardiomyocytes were transduced in vitro
with adenoviral vectors encoding cDNA for
eNOS (AdeNOS) and PGK empty vector. In
contrast to AdPGK-transduced cells,
cardiomyocytes transduced with AdeNOS
increased calcium-dependent NOS activity
(measured by the conversion of
[ 3 H]L-arginine to [ 3 H]L-citrulline) and
produced increased amounts of nitrite.
Cardiomyocytes transduced with AdeNOS
showed diminished endothelin-1
(ET-1)-stimulated protein synthesis as
measured by [ 3 H]-leucine uptake. The
present study demonstrates that
adenovirus-mediated gene transfer of eNOS
to cardiomyocytes results in the expression
of a functional enzyme. Expression of
recombinant eNOS in cardiomyocytes results
in inhibition of ET-1-stimulated protein
synthesis. These findings imply that eNOS
gene transfer to cardiomyocytes may be a
unique mode of increasing local NO
production in the heart.