ABSTRACT
AIM:
To investigate whether KCNE 2 participates in the development of pathological
hypertrophy .
METHODS:
Bidirectional ma-nipulations of KCNE2 expression were performed by adenoviral overexpression of KCNE 2 or knockdown of KCNE2 with
RNA interfer-ence in PE-induced neonatal
rat ventricular
myocytes .Then overexpression of KCNE 2 in
mouse model of
left ventricular hypertrophy in-duced by transverse aortic
constriction (TAC) by ultrasound
microbubble-mediated
gene transfer were used to detect the
therapeutic function of KCNE2 in the development of
hypertrophy .
RESULTS:
KCNE2 expression was significantly decreased in PE-induced hy-pertrophic
cardiomyocytes and in hypertrophic
hearts produced by TAC .Knockdown of KCNE2 in
cardiomyocytes reproduced hypertro-phy, whereas overexpression of KCNE2 attenuated PE-induced
cardiomyocyte hypertrophy .Knockdown of KCNE2 increased
calcineurin activity and nuclear NFAT
protein level , and pretreatment with
nifedipine or
FK 506 attenuated decreased KCNE 2-induced cardiomyo-cyte
hypertrophy .Overexpression of KCNE 2 in
heart by ultrasound
microbubble-mediated
gene transfer suppressed the development of
hypertrophy and activation of
calcineurin-NFAT and MAPK pathways in TAC
mice .
CONCLUSION:
These findings demonstrate that cardiac KCNE2 expression is decreased and contributes to the development of
hypertrophy via activation of
calcineurin -NFAT and MAPK pathways .