Qian Jie-Sheng, Pang Rui-Ping, Zhu Kang-Shun, Liu Da-Yue, Li Zhen-Ran, Deng Chun-yu, Wang Shen-Ming
Department of Vascular Surgery, the first affiliated hospital, Sun Yat-Sen University, Guangdong, PR China.
Cell Physiol Biochem. 2009;24(5-6):461-70. doi: 10.1159/000257485. Epub 2009 Nov 4.
Arterial smooth muscle cell proliferation is a key event in the development of hypertension associated vascular disease. Although previous studies have found that pressure itself can promote cell proliferation and DNA synthesis in vascular smooth muscle cells, the mechanisms are not clear. Recent accumulating evidence indicate that volume-regulated chloride channel plays an important role in the regulation of cell proliferation induced by numerous mitogenic factors. However, whether volume-regulated chloride channel is involved in hypertension-induced vascular smooth muscle cell proliferation remains to be determined. In this study, we found that static pressure promoted rat aortic smooth muscle cell proliferation and cell cycle progression. Static pressure treatment increased volume-regulated chloride currents and ClC-3 expression. Inhibition of chloride channel with pharmacological blockers or knockdown of ClC-3 with ClC-3 antisense transfection attenuated pressure-evoked cell proliferation and cell cycle progression. Static pressure enhanced the production of reactive oxygen species (ROS) in aortic smooth muscle cells. Diphenyleneiodonium (DPI) or apocynin pretreatment inhibited pressure-induced ROS production as well as cell proliferation. Furthermore, DPI or apocynin attenuated the pressure-induced upregulation of ClC-3 protein and hypoosmolarity-activated chloride current. Our data suggest that volume-regulated chloride channel plays a critical role in static pressure-induced cell proliferation and cell cycle progression, suggesting the therapeutic importance of volume-regulated chloride channel for treatment of hypertension attendant vascular complications.
动脉平滑肌细胞增殖是高血压相关血管疾病发展过程中的关键事件。尽管先前的研究发现压力本身可促进血管平滑肌细胞的增殖和DNA合成，但其机制尚不清楚。最近越来越多的证据表明，容积调节性氯通道在多种促有丝分裂因子诱导的细胞增殖调节中起重要作用。然而，容积调节性氯通道是否参与高血压诱导的血管平滑肌细胞增殖仍有待确定。在本研究中，我们发现静水压可促进大鼠主动脉平滑肌细胞增殖和细胞周期进程。静水压处理增加了容积调节性氯电流和ClC-3的表达。用药物阻滞剂抑制氯通道或用ClC-3反义转染敲低ClC-3可减弱压力诱发的细胞增殖和细胞周期进程。静水压增强了主动脉平滑肌细胞中活性氧（ROS）的产生。二苯基碘鎓（DPI）或芹菜素预处理可抑制压力诱导的ROS产生以及细胞增殖。此外，DPI或芹菜素减弱了压力诱导的ClC-3蛋白上调和低渗激活的氯电流。我们的数据表明，容积调节性氯通道在静水压诱导的细胞增殖和细胞周期进程中起关键作用，提示容积调节性氯通道在治疗高血压伴发的血管并发症方面具有重要的治疗意义。
