The Development Of Iso-induced Cardiac Hypertrophy And Anti-hypertrophy Mechanism Of STVNa

Cardiac hypertrophy is a common process of many cardiovascular diseases,which undergoes a transient from compensatory hypertrophy to heart failure.To attenuate or inhibit cardiac hypertrophy is an effective strategy against cardiovascular disease.Isosteviol is hydrolyzed from stevioside,and possesses a broad of biological activities.STVNa is a sodium salt of isosteviol,which have been proved that it has a cardiac protective role against ischemia-reperfusion injury and TAC-induced cardiac hypertrophy.However,the potential anti-hypertrophy effect of isosteviol and isosteviol sodium not yet clear.In the present study,we investigate the development of Iso-induced cardiac hypertrophy and the anti-hypertrophy mechanism of STVNa.1.We investigated the development of Iso-induced cardiac hypertrophy on H9c2 cells for 24,48 and 72 hours.The results revealed that the pathological model was successfully constructed after 48 h treatment of Iso,indicating by the increase of cell surface area,mRNA expression of ANP and ?-MHC.With the developing of cardiac hypertrophy,most significant indicators of cardiac hypertrophy such as ROS and NO signal varies.Experiments showed that cell surface area exhibit a continuously increase while mitochondrial membrane potential(??m)and NO/ROS balanced exhibit a continuously decrease during cardiac hypertrophy process.Interestingly,cell viability conserved on 48 hours and then exhibit a down-regulation on 72 hours,which is combined with thioredoxin 1(Trx1)and peroxiredoxin 2(Prdx2)expression exhibiting a temporary up-regulation and following down-regulation.And we also observed that Trx1 mRNA expression exhibits a continuously decrease while Prdx2 mRNA expression is similar to protein expression.2.We observed the anti-hypertrophy effect of STVNa both in in vivo and in vitro.The results showed that STVNa inhibited Iso-induced cardiac hypertrophy as indicated attenuation of cell size,fetal gene mRNA expression,cell viability,and mitochondrial membrane potential.And then we studied the protection mechanism of STVNa,the results exhibited that STVNa inhibited the increase of ROS induced by Iso treatment.We also found that STVNa treatment elevated Trx1 and Prdx2 mRNA and protein expression both in normal conditions and Iso-induced cardiac hypertrophy.Conclusion: NO/ROS balanced,which is regulated by Trx1 and Prdx2 expression,is important in Iso-induced cardiac hypertrophy.Down-regulation of Trx1 and Prdx2 involve in the cardiac hypertrophy and the transients from compensatory to de-compensatory hypertrophy and then cell apoptosis.STVNa has a cardiac protection on Iso-induced cardiac hypertrophy,and the pharmacological mechanism may be related to the up-regulation of Trx1 and Prdx2 which inhibit the production of cellular ROS.