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However, the involvement of Prx5 in cardiac hypertrophy remains unclear. Therefore, this study is aimed at investigating the role and mechanisms of Prx5 in pathological cardiac hypertrophy and dysfunction. Transverse aortic constriction (TAC) surgery was performed to establish a pressure overload\u2010induced cardiac hypertrophy model. In this study, we found that Prx5 expression was upregulated in hypertrophic hearts and cardiomyocytes. In addition, Prx5 knockdown accelerated pressure overload\u2010induced cardiac hypertrophy and dysfunction in mice by activating oxidative stress and cardiomyocyte apoptosis. Importantly, heart deterioration caused by Prx5 knockdown was related to mitogen\u2010activated protein kinase (MAPK) pathway activation. 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