Transmural pressure drives proliferation of human arterial smooth muscle cells via mechanism associated with NADPH oxidase and Survivin

Abstract

Proliferation of vascular smooth muscle cells (VSMCs) plays an important role in various vascular diseases. Abnormal hemodynamic factors are important stimulus for promoting proliferation of VSMCs. In this study, we show that transmural pressure (TP) promotes the proliferation of human arterial smooth muscle cells (HASMCs) and its related mechanism. HASMCs were treated with different TPs (0,100,120,140,160,180 and 200 mmHg) in a custom-made pressure loading apparatus for 6 h. Results showed that proliferation of HASMCs was significantly promoted when the TP was over 160 mmHg compared with 0 mmHg (atmosphere pressure). In like manner, the expressions of NADPH oxidase 2(Nox2) and Survivin (SVV) and production of intracellular reactive oxygen species (ROS) were all elevated distinctly when TP exceeded 160 mmHg. Moreover, ROS scavenger NAC reduced TP-induced proliferation of HASMCs and expression of SVV largely, and slightly down-regulated expression of NOX2. NOX inhibitor apocynin (Apo) also significantly reduced TP-induced proliferation of HASMCs and expression of SVV and almost completely eliminated TP-induced production of ROS. These results demonstrate that TP drives proliferation of HASMCs via mechanism associated with NOX and SVV.