Abstract
Astragaloside IV is widely used for the treatment of cardiovascular diseases
in China. However, its role in cardiac hypertrophy remains unclear. In this
study, we aim to determine the protective effects of astragaloside IV on
myocardial hypertrophy induced by lipopolysaccharide and to identify their
precise molecular and cellular mechanisms. Cell size, reorganization of
actin filaments, and ANP and BNP mRNA expression were used as indices of
hypertrophy; CaN and GATA-4 expression and the distribution of NFAT-3 in
both cytoplasm and nucleus were determined by Western blot analysis;
Ca2+ transient in Fura-2/AM-loaded cells was measured by Till
image system. Our data demonstrated that lipopolysaccharide challenge
induced cardiac hypertrophy, increased resting Ca2+ transient
level, promoted activation of CaN and GATA-4, and enhanced nuclear
translocation of NFAT-3. Administration of astragaloside IV (16, 32, and
64 µM) 1 h prior to lipopolysaccharide stimulation dose-dependently
attenuated cardiac hypertrophy induced by lipopolysaccharide. Further
studies demonstrated that astragaloside IV inhibited the increment of the
resting intracellular free Ca2+, and its effect was similar to
verapamil. Moreover, astragaloside IV also inhibited the activation of CaN
and GATA-4, and the nuclear translocation of NFAT-3 induced by
lipopolysaccharide. In conclusion, our results revealed that astragaloside
IV had the potential to protect against cardiac hypertrophy through
Ca2+-mediated CaN signaling pathways.
Key words
astragaloside IV - cardiac hypertrophy - calcium - calcineurin
