Overexpression Of Peroxiredoxin-2 Inhibits 2K-1C-induced Myocardial Hypertrophy And Dysfunction In Mice

Objectives Peroxiredoxin-2(Prx-2) is a novel type of antioxidant enzyme. Using prx-2lentiviral transfection and 2 kideny-1 clip(2K-1C) animal model, this study is to explore the precious protective mechanism of Prx-2 on 2K-1C–induced cardiac hypertrophy and dysfunction.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) 2K-1C group(n=9), 5) 2K-1C/vehicle group(n=10), 6)2K-1C/Prx-2 group(n=12). Control or Prx-2 lentiviral vector was transferred into myocardial tissue by direct intraventricular injection 2 weeks before 2K-1C model. systolic blood pressure(SBP) was performed weekly. Using single pressure catheter, cardiac function [parameters for contraction ability: dp/dtmax, dp/dtmax/ip; parameter for relax ability: dp/dtmin; parameters for reserve function: changes before and after Isoproterenol,(?LVPP, ? dp/dtmax, ? dp/dtmax/ip)] was assessed 12 weeks after 2K-1C. The levels of 8-OHd G was detected by immunofluorescence. Western blot was used to evaluate the expressions of Prx-2 and collagen type I and III. Tunel assay was to measure the changes of cell apoptosis in heart.Results 1 The expression of Prx-2 protein after Prx-2 lentiviral transfection was significantly higher than vehicle group [(1.14±0.15) vs(0.17±0.02),P<0.05]. 2 Factorial analysis of variance shown that there was no interaction between 2K-1C and empty lentiviral transfection or between 2K-1C andprx-2 lentiviral transfection on. 3 2K-1C significantly increased SBP, heart weight(HW), left ventricle weight(LVW), collagen type I and III levels, dp/dtmax, dp/dtmax/ip, ? dp/dtmax, ? dp/dtmax/ip, 8-OHd G, apoptosis index, and decreased dp/dtmin and ? dp/dtmin.There was no difference in all parameters between 2K-1C and 2K-1C/vehicle groups. Compared with 2K-1C/vehicle group, the levels of ?dp/dtmax and ?dp/dtmax/ip in 2K-1C/Prx-2 group were markedly increased, and collagen type I and III levels, 8-OHd G and apoptosis index were decreased although SBP,HW, LVW, dp/dtmax, dp/dtmax/ip and dp/dtmin had no changes. 4 The Prx-2 expression was upregulated in sham/Prx-2 and 2K-1C groups compared with sham [(1.95±0.23) vs(0.74±0.17) vs(0.24±0.03),P<0.05], while it didn’t show difference between 2K-1C and2K-1C/vehcle groups. It was further increased in 2K-1C/Prx-2 group in contrast to 2K-1C/vehcle group [(2.17±0.34) vs(0.66±0.13), P<0.05].Conclusions Overexpression of Prx-2 doesn’t inhibit hypertension and myocardial hypertrophy induced by 2K-1C, but it can inhibit cardiac fibrosis and apoptosis as well as enhance the cardiac reserve function, which may be related to the decrease in reactive oxygen specieslevel.