Effect And Mechanism Research Of Peroxiredoxin-2 On Cardiac Hypertrophy Induced By Angiotensin Ⅱ

Objective: Cardiac hypertrophy is an adaptive change of heart in the response to pathological contexts.Patients suffer from reduced life quality and expectancy in the transition from compensated hypertrophy to decompensated heart failure.However,the progress of cardiac hypertrophy is complicated,and the mechanism is still poorly understood.Peroxiredoxin-2(Prdx-2)is recognized as a member of peroxiredoxin(Prdx)family,which has been widely discovered in various organizations.The role of Prdx-2in the development of cardiac hypertrophy remains poorly defined.In this study,we constructed the mouse model of cardiac hypertrophy with the treatment of angiotensin Ⅱ(Ang Ⅱ),aiming to investigate the mechanism of Prdx-2 and explore the potential new therapeutic target in Ang Ⅱ-induced cardiac hypertrophy.Methods:(1)Cardiac hypertrophy model in mice was developed through minipumping of Ang Ⅱ and Prdx-2 was overexpressed by the intraperitoneal injection of human recombinant Prdx-2 twice a week for a total of 4 injections.(2)Cardiac function,cardiomyocyte morphology,cardiac fibrosis,markers of cardiac hypertrophy,cardiomyocyte apoptosis and the expression level of Prdx-2 and VEGF-A were accessed in mice.(3)H9c2 cells were cultured in different concentrations of Ang Ⅱ for 24 or 48 hours.Markers of cardiac hypertrophy were accessed to evaluate an appropriate condition to develop cardiac hypertrophy model in H9c2 cells.Prdx-2 was overexpressed by preconditioned with human recombinant Prdx-2 in H9c2 cells.(4)Expression level of ANP,BNP,Prdx-2,and VEGF-A were accessed in H9c2 cells.Results:(1)Cardiac hypertrophy model was successfully developed by Ang Ⅱ in mice and cardiac dysfunction,myocardial fibrosis and cardiomyocyte morphology were observed in Ang Ⅱ-induced hypertrophy in mice.(2)Prdx-2 was upregulated in AngⅡ-induced cardiac hypertrophy.Systemic administration of Prdx-2 aggravated cardiac hypertrophy while alleviated myocardial apoptosis and myocardial fibrosis and upregulated the expression of CD31 and VEGF-A in mice.(3)Treatment of Ang Ⅱupregulated markers of cardiac hypertrophy in H9c2 cell and cardiac hypertrophy was successfully developed in H9c2 cell.(4)Prdx-2 was upregulated in cardiac hypertrophy and markers of cardiac hypertrophy and the treatment of human recombinant Prdx-2further upregulated the expression level of VEGF-A in H9c2 cells.Conclusion: Prdx-2 aggravated Ang Ⅱ-induced cardiac hypertrophy and promoted the expression of VEGF-A and the capacity of pro-angiogenesis.