Huang Kun, Gao Lu, Yang Ming, Wang Jiliang, Wang Zheng, Wang Lin, Wang Guobin, Li Huili
Institution of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan, Hubei, China.
Department of Cardiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China.
Int J Biochem Cell Biol. 2017 Aug;89:6-15. doi: 10.1016/j.biocel.2017.05.020. Epub 2017 May 15.
Angiotensin (Ang) Ⅱ-induced cardiac hypertrophy can deteriorate to heart failure, a leading cause of mortality. Endogenous Cathepsin V (CTSV) has been reported to be cardioprotective against hypertrophy. However, little is known about the effect of exogenous CTSV on cardiac hypertrophy. We used the human cardiomyocytes HCM as a cell model to investigate the effects of exogenous CTSV on Ang Ⅱ-induced cardiac cell hypertrophy. Cell surface area and expression of classical markers of hypertrophy were analyzed. We further explored the mechanism of CTSV cardioprotective by assessing the levels and activities of PI3K/Akt/mTOR and MAPK signaling pathway proteins. We found that pre-treating cardiomyocytes with CTSV could significantly inhibit Ang Ⅱ-induced hypertrophy. The mRNA expression of hypertrophy markers ANP, BNP and β-MHC was obviously elevated in Ang Ⅱ-treated cardiac cells. Whereas, exogenous CTSV effectively halted this elevation. Further study revealed that the protective effects of exogenous CTSV might be mediated by repressing the phosphorylation of proteins in the PI3K/Akt/mTOR and MAPK pathways. Based on our results, we concluded that exogenous CTSV inhibited Ang Ⅱ-induced hypertrophy in HCM cells by inhibiting PI3K/Akt/mTOR. This study provides experimental evidence for the application of CTSV protein for the treatment of cardiac hypertrophy.
血管紧张素（Ang）Ⅱ诱导的心脏肥大可恶化为心力衰竭，而心力衰竭是导致死亡的主要原因。据报道，内源性组织蛋白酶V（CTSV）对肥大具有心脏保护作用。然而，关于外源性CTSV对心脏肥大的影响知之甚少。我们使用人类心肌细胞HCM作为细胞模型，研究外源性CTSV对AngⅡ诱导的心脏细胞肥大的影响。分析了细胞表面积和肥大经典标志物的表达。我们通过评估PI3K/Akt/mTOR和MAPK信号通路蛋白的水平和活性，进一步探讨了CTSV心脏保护的机制。我们发现，用CTSV预处理心肌细胞可显著抑制AngⅡ诱导的肥大。在AngⅡ处理的心脏细胞中，肥大标志物ANP、BNP和β-MHC的mRNA表达明显升高。然而，外源性CTSV有效地阻止了这种升高。进一步的研究表明，外源性CTSV的保护作用可能是通过抑制PI3K/Akt/mTOR和MAPK途径中蛋白质的磷酸化来介导的。基于我们的结果，我们得出结论，外源性CTSV通过抑制PI3K/Akt/mTOR来抑制HCM细胞中AngⅡ诱导的肥大。本研究为CTSV蛋白用于治疗心脏肥大提供了实验证据。
