Ubiquitin-specific protease 2 (USP2) is an important member of the deubiquitination system. GEO dataset revealed that USP2 was downregulated in the hearts under pressure overload. However, the cardiomyocyte-specific function of USP2 in the setting of pressure overload is unknown. In the current study, a mouse model of pressure overload was induced by transverse aortic constriction (TAC, 2 weeks). Overexpression of USP2 in the heart was conducted by AAV9 infection. Changes in heart histology were detected by Masson’s trichrome staining and hematoxylin-eosin staining (H&E). Echocardiography was used to assess cardiac function. The size of cardiomyocytes was examined by wheat germ agglutinin (WGA) staining. Cardiac oxidative stress was detected by dihydroethidine staining. Our results showed that USP2 was downregulated in the cardiomyocytes following 2 weeks of TAC. Overexpression of cardiac USP2 preserved ventricular function following 2 weeks of TAC. Overexpression of cardiac USP2 inhibited TAC-induced cardiac remodeling, by suppressing cardiac hypertrophy, inhibiting inflammatory responses and fibrosis, and attenuating oxidative stress. Our findings reveal a previously unrecognized role of USP2 in regulating pressure overload-induced cardiac remodeling.

中文翻译：

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泛素特异性蛋白酶 2 (USP2) 在心脏抑制压力超负荷诱导的心脏重构中的过度表达。

泛素特异性蛋白酶 2 (USP2) 是去泛素化系统的重要成员。GEO 数据集显示 USP2 在压力超负荷下在心脏中被下调。然而，USP2 在压力超负荷情况下的心肌细胞特异性功能尚不清楚。在当前的研究中，通过横向主动脉收缩（TAC，2 周）诱导了压力超负荷的小鼠模型。USP2 在心脏中的过度表达是通过 AAV9 感染进行的。通过马森三色染色和苏木精-伊红染色 (H&E) 检测心脏组织学的变化。超声心动图用于评估心脏功能。通过小麦胚芽凝集素（WGA）染色检查心肌细胞的大小。通过二氢乙啶染色检测心脏氧化应激。我们的结果表明，在 TAC 2 周后，心肌细胞中的 USP2 下调。在 TAC 治疗 2 周后，心脏 USP2 的过度表达保留了心室功能。心脏 USP2 的过度表达通过抑制心脏肥大、抑制炎症反应和纤维化以及减弱氧化应激来抑制 TAC 诱导的心脏重塑。我们的研究结果揭示了 USP2 在调节压力超负荷诱导的心脏重塑方面的先前未被认识的作用。