Potential mechanism of myocardium apoptosis of right ventricle in rat under chronic hypoxia

AIM:We used an animal model of chronic hypoxia to mimic right ventricular hypertrophy and try to study the potential mechanism of myocardium apoptosis of right heart in rat under chronic hypoxia. METHODS: Rat hypoxia models were established by exposing the rats to normobaric chronic hypoxia (oxygen levels were maintained at 9.5%-10.5%). Sixty rats were separated into two groups: one exposed to hypoxia and the other serving as control. Ten rats, randomly selected from each group were killed at 14, 21, 28 d after hypoxia. The apoptosis was determined. The changes of RV weight to left ventricle and interventricular septum weight ratio［RV/(LV+S)］, the RV weight to body weight ratio (RV/BW) were also observed. The β-MHC, bcl-2 and bad mRNA levels in right ventricle were detected by semi-quantitative RT-PCR assays and expression of β-MHC, Bcl-2 and Bad protein levels were detected by Western blotting.RESULTS: The RV/(LV+S), RV/BW and apoptosis index in chronic hypoxia group were higher than those in normal control group (P<0.01). The results of RT-PCR and Western blotting showed that β-MHC mRNA levels and protein levels in chronic hypoxia group were higher than those in normal control group (P<0.01). The rate of apoptosis, the RV/(LV+S), RV/BW and the expression of β-MHC in hypoxia group all increased with time. The bcl-2 mRNA and Bcl-2 protein expressions in chronic hypoxia group were lower compared with control group at 14, 21 and 28 d (P<0.05). In contrast, no significant change of bad mRNA and Bad protein expressions in chronic hypoxia group were observed compared with control group (P>0.05). Finally, a decreased bcl-2/bad〖STBZ〗 ratio in chronic hypoxia group was found compared with control group (P<0.05). Both the expression of bcl-2 and the bcl-2/bad ratio decreased with time (P<0.05).CONCLUSION:These data demonstrate that chronic hypoxia may induce right ventricular hypertrophy, as well as cardiomyocytes apoptosis. Furthermore, apoptosis in hypertrophic cardiomyocytes induced by hypoxia is mainly due to the inhibition of bcl-2 expression and decrease of bcl-2/bad ratio.