Ma Yanzhuo, Kong Lingfeng, Qi Shuying, Wang Dongmei
Department of Cardiology, Bethune International Peace Hospital, Shijiazhuang 050000, China.
Department of Cardiology, Bethune International Peace Hospital, Shijiazhuang 050000, China Hebei Medical University, Shijiazhuang 050011, China.
Acta Biochim Biophys Sin (Shanghai). 2016 Apr;48(4):378-84. doi: 10.1093/abbs/gmw009. Epub 2016 Mar 2.
Thel-type Ca(2+)current (ICa,l) plays a crucial role in shaping action potential and is involved in cardiac arrhythmia. Statins have been demonstrated to contribute to anti-apoptotic and anti-arrhythmic effects in the heart. Here, we examined whether atorvastatin regulates theICa,land cell injury induced by angiotensin II (AngII) as well as the putative intracellular cascade responsible for the effects. Cultured neonatal rat ventricular myocytes were incubated with AngII for 24 h, and then cell injury and expression levels of Nox2/gp91(phox), p47(phox) ,and Cav1.2 were analyzed. In addition,ICa,lwas recorded using the whole-cell patch-clamp technique, and mechanisms of atorvastatin actions were also investigated. It was found that the number of apoptotic cardiomyocytes was increased and cell viability was significantly decreased after AngII administration. AngII also augmented the expressions of Nox2/gp91(phox)and p47(phox)compared with control cardiomyocytes. Exposure to AngII evokedICa,lin a voltage-dependent manner without affecting theI-Vrelationship. In addition, AngII enhanced membrane Cav1.2 expression. These effects were abolished in the presence of the reactive oxygen species (ROS) scavenger, manganese (III)-tetrakis 4-benzoic acid porphyrin [Mn(III)TBAP], or the 3-hydroxy-3-methylglutaryl-CoA reductase inhibitor, atorvastatin. These results suggested that atorvastatin mediates cardioprotection against arrhythmias and cell injury by controlling the AngII-ROS cascade.
L型钙电流（ICa,l）在动作电位形成中起关键作用，并与心律失常有关。他汀类药物已被证明对心脏具有抗凋亡和抗心律失常作用。在此，我们研究了阿托伐他汀是否能调节血管紧张素II（AngII）诱导的ICa,l和细胞损伤，以及负责这些作用的潜在细胞内信号通路。将培养的新生大鼠心室肌细胞与AngII孵育24小时，然后分析细胞损伤以及Nox2/gp91(phox)、p47(phox)和Cav1.2的表达水平。此外，使用全细胞膜片钳技术记录ICa,l，并研究阿托伐他汀的作用机制。结果发现，给予AngII后，凋亡心肌细胞数量增加，细胞活力显著降低。与对照心肌细胞相比，AngII还增加了Nox2/gp91(phox)和p47(phox)的表达。暴露于AngII以电压依赖性方式诱发ICa,l，而不影响电流-电压关系。此外，AngII增强了细胞膜Cav1.2的表达。在活性氧（ROS）清除剂锰（III）-四（4-苯甲酸）卟啉[Mn(III)TBAP]或3-羟基-3-甲基戊二酰辅酶A还原酶抑制剂阿托伐他汀存在的情况下，这些作用被消除。这些结果表明，阿托伐他汀通过控制AngII-ROS信号级联介导对心律失常和细胞损伤的心脏保护作用。
