Overexpression Of Peroxiredoxin-2 Inhibits DOCA-Salt-Induced Myocardial Hypertrophy And Dysfunction In Mice

Objectives Peroxiredoxin-2（Prx-2） is a novel type of antioxidant enzyme. Using prx-2 lentiviral transfection and DOCA-Salt animal model, this study is to explore the precious protective mechanism of Prx-2 on DOCA-Salt–induced cardiac hypertrophy and dysfunction by observing the changes of DOCA-Salt induced systolic blood pressure, cardiac hypertrophy, type I and type III collagen, cardiac function, cell apoptosis and reactive oxygen species.Methods Male C57BL/6 mice with 8 weeks ages were randomly divided into 1) sham group（n=10）, 2) sham/vehicle group（control lentiviral vector, n=9）, 3) sham/Prx-2 group（Prx-2 lentiviral vector, n=10）, 4) DOCA group（n=9）, 5) DOCA/vehicle group（n=10）, 6) DOCA/Prx-2 group（n=12）. Control or Prx-2 lentiviral vector was transferred into myocardial tissue by direct intraventricular injection 2 weeks before DOCA-Salt model. Two weeks after making DOCA-Salt model. After a week, Systolic blood pressure（SBP） was measured once a week. Using single pressure catheter, cardiac function [parameters for contraction ability: dp/dt_max, dp/dt_max/ip; parameter for relax ability: dp/dt_min; parameters for reserve function: changes before and after Isoproterenol,(（?）dp/dt_min, （?）dp/dt_max, （?）dp/dt_max/ip)] was assessed 12 weeks after DOCA-Salt. The levels of 8-OHd G expression was detected by immunofluorescence. Western blot was used to evaluate the expressions of Prx-2、collagen type I and III 、ASK1、p-ASK1、p38 and p-p38. Tunel assay was to measure the changes of cell apoptosis in heart. Spectrophotometric method measured the activity values of Caspase-3.Results 1 The expression of Peroxiredoxin-2 protein after Peroxiredoxin-2 lentiviral transfection was significantly higher than vehicle group（P<0.01）. 2 Compared with the sham group, DOCA significantly increased SBP, heart weight（HW）, left ventricle weight（LVW）, collagen type I and III levels, 8-OHd G, apoptosis index, expression of p-ASK1 and p-p38 levels,the activity values of Caspase-3（P<0.05）, but （?）dp/dt_max, （?）dp/dt_max/ip and （?）dp/dt_min had no change. There was no difference in all parameters between DOCA and DOCA/vehicle groups（P>0.05）. Compared with DOCA/vehicle group, There was no significant difference in SBP, whole heart mass and left ventricular mass in DOCA/Prx-2 group（P>0.05）; But the levels of （?）dp/dt_max and （?）dp/dt_max/ip in DOCA/Prx-2 group were obviously increased, and collagen type I and III levels, 8-OHd G, expression of p-ASK1 and p-p38 levels, the activity values of Caspase-3 and apoptosis index were decreased（P<0.05）. 4 The Peroxiredoxin-2 expression was upregulated in sham/Prx-2 and DOCA groups compared with sham（P<0.05）, while it didn’t show difference between DOCA and DOCA/vehcle groups（P>0.05）. It was further increased in DOCA/Prx-2 group in contrast to DOCA/vehcle group（P<0.05）.Conclusions 1 Over expression of Peroxiredoxin-2 doesn’t inhibit hypertension and myocardial hypertrophy induced by DOCA-Salt,; 2 Over expression of Peroxiredoxin-2 can inhibit myocardial apoptosis and cardiac fibrosis by reducing the levels of reactive oxygen species, so as to enhance the cardiac reserve function; 3 ASK1/p38/Caspase-3 pathway plays an important role in the process of inhibiting the apoptosis of myocardial cells by reactive oxygen species.