Lin Li, Xu Jianfeng, Ye Yong, Ge Junbo, Zou Yunzeng, Liu Xuebo
*Department of Cardiovascular Medicine, East Hospital, Tongji University School of Medicine, Shanghai, China; and †Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital and Institute of Biomedical Sciences, Fudan University, Shanghai, China.
J Cardiovasc Pharmacol. 2015 Jan;65(1):1-7. doi: 10.1097/FJC.0000000000000122.
Mechanical stress can induce cardiac hypertrophy and autophagy. Recently, it has been reported that nitric oxide donors inhibited autophagy in human chondrocytes. Therefore, the effect of isosorbide dinitrate (ISDN) on cardiac hypertrophy and autophagy induced by mechanical stress was investigated in this study. A 48-hour mechanical stretch and a 4-week transverse aortic constriction were performed to induce cardiomyocyte hypertrophy in vitro and in vivo, respectively, before the assessment of myocardial autophagy using LC3b-II. ISDN was found to significantly reduce mechanical stretch-induced LC3b-II upregulation. Furthermore, mechanical stress was shown to upregulate angiotensin II (AngII) type 1 (AT1) receptor expression in both cultured cardiomyocytes and in mouse hearts, whereas ISDN was demonstrated to significantly suppress the upregulation of the AT1 receptor. It was concluded that ISDN could inhibit mechanical stress-induced cardiac hypertrophy and autophagy through the downregulation of AT1 receptor expression.
机械应力可诱导心肌肥大和自噬。最近，有报道称一氧化氮供体可抑制人软骨细胞中的自噬。因此，本研究探讨了硝酸异山梨酯（ISDN）对机械应力诱导的心肌肥大和自噬的影响。在使用LC3b-II评估心肌自噬之前，分别进行了48小时的机械拉伸和4周的主动脉缩窄，以在体外和体内诱导心肌细胞肥大。发现ISDN可显著降低机械拉伸诱导的LC3b-II上调。此外，机械应力显示可上调培养的心肌细胞和小鼠心脏中血管紧张素II（AngII）1型（AT1）受体的表达，而ISDN被证明可显著抑制AT1受体的上调。得出的结论是，ISDN可通过下调AT1受体表达来抑制机械应力诱导的心肌肥大和自噬。
